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Sample records for c-c motif receptor

  1. Functional interaction between angiotensin II receptor type 1 and chemokine (C-C Motif) receptor 2 with implications for chronic kidney disease

    OpenAIRE

    Mohammed Akli Ayoub; Yuan Zhang; Kelly, Robyn S.; Heng B See; Johnstone, Elizabeth K.M.; McCall, Elizabeth A.; Williams, James H; Kelly, Darren J.; Pfleger, Kevin D.G.

    2015-01-01

    Understanding functional interactions between G protein-coupled receptors is of great physiological and pathophysiological importance. Heteromerization provides one important potential mechanism for such interaction between different signalling pathways via macromolecular complex formation. Previous studies suggested a functional interplay between angiotensin II receptor type 1 (AT1) and Chemokine (C-C motif) Receptor 2 (CCR2). However the molecular mechanisms are not understood. We investiga...

  2. Inhibition of chemokine (C-C motif receptor 7 sialylation suppresses CCL19-stimulated proliferation, invasion and anti-anoikis.

    Directory of Open Access Journals (Sweden)

    Mei-Lin Su

    Full Text Available Chemokine (C-C motif receptor 7 (CCR7 is involved in lymph-node homing of naive and regulatory T cells and lymphatic metastasis of cancer cells. Sialic acids comprise a group of monosaccharide units that are added to the terminal position of the oligosaccharide chain of glycoproteins by sialyation. Recent studies suggest that aberrant sialylation of receptor proteins contributes to proliferation, motility, and drug resistance of cancer cells. In this study, we addressed whether CCR7 is a sialylated receptor protein and tried to elucidate the effect of sialylation in the regulation of signal transduction and biological function of CCR7. Our results demonstrated that α-2, 3-sialyltransferase which catalyze sialylation reaction in vivo was overexpressed in breast tumor tissues and cell lines. Lectin blot analysis clearly demonstrated that CCR7 receptor was sialyated in breast cancer cells. Chemokine (C-C motif ligand 19 (CCL19, the cognate ligand for CCR7, induced the activation of extracellular signal-regulated kinase (ERK and AKT signaling and increased the expression of cell cycle regulatory proteins and proliferation of breast cancer cells. When cells were pre-treated with a sialyltransferase inhibitor AL10 or sialidase, CCL19-induced cell growth was significantly suppressed. CCL19 also increased invasion and prevented anoikis by up-regulating pro-survival proteins Bcl-2 and Bcl-xL. Inhibition of sialylation by AL10 totally abolished these effects. Finally, we showed that AL10 inhibited tumorigenicity of breast cancer in experimental animals. Taken together, we demonstrate for the first time that CCR7 receptor is a sialylated protein and sialylation is important for the paracrine stimulation by its endogenous ligand CCL19. In addition, inhibition of aberrant sialylation of CCR7 suppresses proliferation and invasion and triggers anoikis in breast cancer cells. Targeting of sialylation enzymes may be a novel strategy for breast cancer treatment.

  3. Functional interaction between angiotensin II receptor type 1 and chemokine (C-C motif receptor 2 with implications for chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Mohammed Akli Ayoub

    Full Text Available Understanding functional interactions between G protein-coupled receptors is of great physiological and pathophysiological importance. Heteromerization provides one important potential mechanism for such interaction between different signalling pathways via macromolecular complex formation. Previous studies suggested a functional interplay between angiotensin II receptor type 1 (AT1 and Chemokine (C-C motif Receptor 2 (CCR2. However the molecular mechanisms are not understood. We investigated AT1-CCR2 functional interaction in vitro using bioluminescence resonance energy transfer in HEK293 cells and in vivo using subtotal-nephrectomized rats as a well-established model for chronic kidney disease. Our data revealed functional heteromers of these receptors resulting in CCR2-Gαi1 coupling being sensitive to AT1 activation, as well as apparent enhanced β-arrestin2 recruitment with agonist co-stimulation that is synergistically reversed by combined antagonist treatment. Moreover, we present in vivo findings where combined treatment with AT1- and CCR2-selective inhibitors was synergistically beneficial in terms of decreasing proteinuria, reducing podocyte loss and preventing renal injury independent of blood pressure in the subtotal-nephrectomized rat model. Our findings further support a role for G protein-coupled receptor functional heteromerization in pathophysiology and provide insights into previous observations indicating the importance of AT1-CCR2 functional interaction in inflammation, renal and hypertensive disorders.

  4. A novel motif identified in dependence receptors.

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    Gabriel del Rio

    Full Text Available Programmed cell death signaling is a critical feature of development, cellular turnover, oncogenesis, and neurodegeneration, among other processes. Such signaling may be transduced via specific receptors, either following ligand binding-to death receptors-or following the withdrawal of trophic ligands-from dependence receptors. Although dependence receptors display functional similarities, no common structural domains have been identified. Therefore, we employed the Multiple Expectation Maximization for Motif Elicitation and the Motif Alignment and Search Tool software programs to identify a novel transmembrane motif, dubbed dependence-associated receptor transmembrane (DART motif, that is common to all described dependence receptors. Of 3,465 human transmembrane proteins, 25 (0.7% display the DART motif. The predicted secondary structure features an alpha helical structure, with an unusually high percentage of valine residues. At least four of the proteins undergo regulated intramembrane proteolysis. To date, we have not identified a function for this putative domain. We speculate that the DART motif may be involved in protein processing, interaction with other proteins or lipids, or homomultimerization.

  5. Vascular Stem/Progenitor Cell Migration Induced by Smooth Muscle Cell-Derived Chemokine (C-C Motif) Ligand 2 and Chemokine (C-X-C motif) Ligand 1 Contributes to Neointima Formation.

    Science.gov (United States)

    Yu, Baoqi; Wong, Mei Mei; Potter, Claire M F; Simpson, Russell M L; Karamariti, Eirini; Zhang, Zhongyi; Zeng, Lingfang; Warren, Derek; Hu, Yanhua; Wang, Wen; Xu, Qingbo

    2016-09-01

    Recent studies have shown that Sca-1(+) (stem cell antigen-1) stem/progenitor cells within blood vessel walls may contribute to neointima formation, but the mechanism behind their recruitment has not been explored. In this work Sca-1(+) progenitor cells were cultivated from mouse vein graft tissue and found to exhibit increased migration when cocultured with smooth muscle cells (SMCs) or when treated with SMC-derived conditioned medium. This migration was associated with elevated levels of chemokines, CCL2 (chemokine (C-C motif) ligand 2) and CXCL1 (chemokine (C-X-C motif) ligand 1), and their corresponding receptors on Sca-1(+) progenitors, CCR2 (chemokine (C-C motif) receptor 2) and CXCR2 (chemokine (C-X-C motif) receptor 2), which were also upregulated following SMC conditioned medium treatment. Knockdown of either receptor in Sca-1(+) progenitors significantly inhibited cell migration. The GTPases Cdc42 and Rac1 were activated by both CCL2 and CXCL1 stimulation and p38 phosphorylation was increased. However, only Rac1 inhibition significantly reduced migration and p38 phosphorylation. After Sca-1(+) progenitors labeled with green fluorescent protein (GFP) were applied to the adventitial side of wire-injured mouse femoral arteries, a large proportion of GFP-Sca-1(+) -cells were observed in neointimal lesions, and a marked increase in neointimal lesion formation was seen 1 week post-operation. Interestingly, Sca-1(+) progenitor migration from the adventitia to the neointima was abrogated and neointima formation diminished in a wire injury model using CCL2(-/-) mice. These findings suggest vascular stem/progenitor cell migration from the adventitia to the neointima can be induced by SMC release of chemokines which act via CCR2/Rac1/p38 and CXCR2/Rac1/p38 signaling pathways. Stem Cells 2016;34:2368-2380.

  6. Chemokine (C-C motif ligand 20, a potential biomarker for Graves' disease, is regulated by osteopontin.

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    Xiaoli Li

    Full Text Available CONTEXT: Graves' disease (GD is a common autoimmune disease involving the thyroid gland. The altered balance of pro- and anti-inflammatory cytokines plays an important role in the pathogenesis of GD. Chemokine (C-C motif ligand 20 (CCL20 is important for interleukin-17 (IL-17 signal activation and a potent chemoattractant for Th17 cells. Meanwhile, Osteopontin (OPN, a broadly expressed pleiotropic cytokine, has been implicated in GD through inducing Th1-involved response to enhance the production of proinflammatory cytokines and chemokines, but little is known about the role of OPN in regulating CCL20 and IL-17 signaling. OBJECTIVE: This study sought to explore the possibility of CCL20 level as a biomarker for GD, as well as investigate the role of OPN in regulating CCL20 production. METHODS: Fifty untreated GD patients, fifteen euthyroid GD patients, twelve TRAb-negative GD patients and thirty-five healthy control donors were recruited. OPN, CCL20 and other clinical GD diagnosis parameters were measured. CD4+T cells were isolated from peripheral blood mononuclear cells (PBMCs using antibody-coated magnetic beads. Enzyme-linked immune-sorbent assay and quantitative polymerase chain reaction were used to determine CCL20 expression level. RESULTS: We found that the plasma CCL20 level was enhanced in GD patients and decreased in euthyroid and TRAb-negative GD patients. In addition, CCL20 level correlated with GD clinical diagnostic parameters and plasma OPN level. Moreover, we demonstrated that recombinant OPN and plasma from untreated GD patients increased the expression of CCL20 in CD4+T cells, which could be blocked by OPN antibody. Furthermore, we found that the effect of OPN on CCL20 expression was mediated by β3 integrin receptor, IL-17, NF-κB and MAPK pathways. CONCLUSIONS: These results demonstrated that CCL20 might serve as a biomarker for GD and suggested the possible role of OPN in induction of CCL20 expression.

  7. Chemokine signaling involving chemokine (C-C motif) ligand 2 plays a role in descending pain facilitation

    Institute of Scientific and Technical Information of China (English)

    Wei Guo; Hu Wang; Shiping Zou; Ronald Dubner; Ke Ren

    2012-01-01

    Objective Despite accumulating evidence on a role of immune cells and their associated chemicals in mechanisms of pain,few studies have addressed the potential role of chemokines in the descending facilitation of persistent pain.The present study was undertaken to test the hypothesis that the chemokine (C-C motif) ligand 2 (CCL2) (commonly known as monocyte chemoattractant protein-1) signaling in the rostral ventromedial medulla (RVM),a pivotal structure in brainstem pain modulatory circuitry,is involved in descending pain facilitation in rats.Methods An L5 spinal nerve ligation (SNL) was produced in rats under pentobarbital anesthesia.Western blot and immunohistochemistry were used to detect the expression levels of CCL2 and CCL2 receptor (CCR2),and examine their distributions compared with the neuronal marker NeuN as well as glial markers glial fibrillary acidic protein (GFAP,astroglial) and CD11b (microglial),respectively.Results SNL induced an increase in CCL2 expression in the RVM,and this returned to the control level at 4 weeks after injury.The induced CCL2 colocalized with NeuN,but not with GFAP and CD11b.CCR2 was also upregulated by SNL in the RVM,and this increase lasted for at least 4 weeks.CCR2 was colocalized with CD1 1b but not GFAP.Few RVM neurons also exhibited CCR2 staining.Neutralizing CCL2 with an anti-CCL2 antibody (0.2-20 ng) or injecting RS-102895 (0.1-10 pmol),a CCR2b chemokine receptor antagonist,into the RVM on day 1 after SNL,significantly attenuated the established thermal and mechanical hypersensitivity.In addition,injection of recombinant rat CCL2 (0.03-3pmol) into the RVM induced dose-dependent hyperalgesia,which was prevented by pretreatment with RS-102895 (10pmol).Interleukin-1β (IL-1β),a potent inducer of neuronal CCL2,was also selectively upregulated in RVM reactive astrocytes.Injection of IL-1β (120 fmol) into the RVM induced behavioral hyperalgesia,which was blocked by RS-102895(10 pmol).However,an IL-1 receptor antagonist (3

  8. The chemokine (C-C motif) ligand protein synthesis inhibitor bindarit prevents cytoskeletal rearrangement and contraction of human mesangial cells.

    Science.gov (United States)

    Paccosi, Sara; Giachi, Matelda; Di Gennaro, Paola; Guglielmotti, Angelo; Parenti, Astrid

    2016-09-01

    Intraglomerular mesangial cells (MCs) maintain structural and functional integrity of renal glomerular microcirculation and homeostasis of mesangial matrix. Following different types of injury, MCs change their phenotype upregulating the expression of α-smooth muscle actin (α-SMA), changing contractile abilities and increasing the production of matrix proteins, chemokines and cytokines. CCL2 is a chemokine known to be involved in the pathogenesis of renal diseases. Its glomerular upregulation correlates with the extent of renal damage. Bindarit is an indazolic derivative endowed with anti-inflammatory activity when tested in experimental diseases. It selectively inhibits the synthesis of inflammatory C-C chemokines including CCL2, CCL7 and CCL8. This work aims to analyse bindarit effects on ET1-, AngII- and TGFβ-induced mesangial cell dysfunction. Bindarit significantly reduced AngII-, ET1- and TGFβ-induced α-SMA upregulation. In a collagen contraction assay, bindarit reduced AngII-, ET1- and TGFβ-induced HRMC contraction. Within 3-6h stimulation, vinculin organization and phosphorylation was significantly impaired by bindarit in AngII-, ET1- and TGFβ-stimulated cells without any effect on F-actin distribution. Conversely, p38 phosphorylation was not significantly inhibited by bindarit. Our data strengthen the importance of CCL2 on ET-1, AngII- and TGFβ-induced mesangial cell dysfunction, adding new insights into the cellular mechanisms responsible of bindarit protective effects in human MC dysfunction. PMID:27309675

  9. The WSXWS motif in cytokine receptors is a molecular switch involved in receptor activation

    DEFF Research Database (Denmark)

    Dagil, Robert; Knudsen, Maiken J.; Olsen, Johan Gotthardt;

    2012-01-01

    The prolactin receptor (PRLR) is activated by binding of prolactin in a 2:1 complex, but the activation mechanism is poorly understood. PRLR has a conserved WSXWS motif generic to cytokine class I receptors. We have determined the nuclear magnetic resonance solution structure of the membrane...

  10. Distinct recognition modes of FXXLF and LXXLL motifs by the androgen receptor.

    NARCIS (Netherlands)

    H.J. Dubbink (Erik Jan); R. Hersmus (Remko); C.S. Verma (Chandra); H.A.G.M. van der Korput (Hetty); C.A. Berrevoets (Cor); J. van Tol (Judith); A.C.J. Ziel-van der Made (Angelique); A.O. Brinkmann (Albert); A.C. Pike (Ashley); J. Trapman (Jan)

    2004-01-01

    textabstractAmong nuclear receptors, the androgen receptor (AR) is unique in that its ligand-binding domain (LBD) interacts with the FXXLF motif in the N-terminal domain, resembling coactivator LXXLL motifs. We compared AR- and estrogen receptor alpha-LBD interactions of the wild-t

  11. C-C chemokine receptor-7 mediated endocytosis of antibody cargoes into intact cells

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    Xavier eCharest-Morin

    2013-09-01

    Full Text Available The C-C chemokine receptor-7 (CCR7 is a G protein coupled receptor that has a role in leukocyte homing, but that is also expressed in aggressive tumor cells. Preclinical research supports that CCR7 is a valid target in oncology. In view of the increasing availability of therapeutic monoclonal antibodies that carry cytotoxic cargoes, we studied the feasibility of forcing intact cells to internalize known monoclonal antibodies by exploiting the cycle of endocytosis and recycling triggered by the CCR7 agonist CCL19. Firstly, an anti-CCR7 antibody (CD197; clone 150503 labeled surface recombinant CCR7 expressed in intact HEK 293a cells and the fluorescent antibody was internalized following CCL19 treatment. Secondly, a recombinant myc-tagged CCL19 construction was exploited along the anti-myc monoclonal antibody 4A6. The myc-tagged ligand was produced as a conditioned medium of transfected HEK 293a cells that contained the equivalent of 430 ng/ml of immunoreactive CCL19 (average value, ELISA determination. CCL19-myc, but not authentic CCL19, carried the fluorophore-labeled antibody 4A6 into other recipient cells that expressed recombinant CCR7 (microscopy, cytofluorometry. The immune complexes were apparent in endosomal structures, colocalized well with the small GTPase Rab5 and progressed toward Rab7-positive endosomes. A dominant negative form of Rab5 (GDP-locked inhibited this endocytosis. Further, endosomes in CCL19-myc- or CCL19-stimulated cells were positive for β-arrestin2, but rarely for β-arrestin1. Following treatment with CCL19-myc and the 4A6 antibody, the melanoma cell line A375 that expresses endogenous CCR7 was specifically stained using a secondary peroxidase-conjugated antibody. Agonist-stimulated CCR7 can transport antibody-based cargoes, with possible therapeutic applications in oncology.

  12. Human C-C chemokine receptor 3 monoclonal antibody inhibits pulmonary inflammation in allergic mice

    Institute of Scientific and Technical Information of China (English)

    Kai WANG; Hua-hao SHEN; Wen LI; Hua-qiong HUANG

    2007-01-01

    Aim:To evaluate the effect of C-C chemokine receptor 3 (CCR3) blockade on pulmonary inflammation and mucus production in allergic mice. Methods:We used the synthetic peptide of the CCR3 NH2-terminal as the immunizing antigen and generated murine monoclonal antibody against the human CCR3. In addition,the generated antibody was administered to mice sensitized and challenged with ovalbumin. The inflammatory cells in bronchoalveolar lavage,cytokine levels,pulmonary histopathology,and mucus secretion were examined. Results:The Western blotting analysis indicated that the generated antibody bound to CCR3 specifically. The allergic mice treated with the antihuman CCR3 antibody exhibited a significant reduction of pulmonary inflammation accompanied with the alteration of cytokine. Conclusion:The antibody we generated was specific to CCR3. The inhibition of airway inflammation and mucus overproduction by the antibody suggested that the blockade of CCR3 is an appealing therapeutical target for asthma. The present research may provide an experimental basis for the further study of this agent.

  13. Changes in plasma chemokine C-C motif ligand 2 levels during treatment with eicosapentaenoic acid predict outcome in patients undergoing surgery for colorectal cancer liver metastasis

    Science.gov (United States)

    Volpato, Milene; Perry, Sarah L; Marston, Gemma; Ingram, Nicola; Cockbain, Andrew J.; Burghel, Heather; Jake, Mann; Lowes, David; Wilson, Erica; Droop, Alastair; Randerson-Moor, Juliette; Coletta, P Louise; Hull, Mark A

    2016-01-01

    The mechanism of the anti-colorectal cancer (CRC) activity of the omega-3 fatty acid eicosapentaenoic acid (EPA) is not understood. We tested the hypothesis that EPA reduces expression of chemokine C-C motif ligand 2 (CCL2), a pro-inflammatory chemokine with known roles in metastasis. We measured CCL2 in clinical samples from a randomized trial of EPA in patients undergoing liver surgery for CRC liver metastasis (LM) and preclinical models. Genome-wide transcriptional profiling of tumors from EPA-treated patients was performed. EPA decreased CCL2 synthesis by CRC cells in a dose-dependent manner. CCL2 was localized to malignant epithelial cells in human CRCLM. EPA did not reduce CCL2 content in human or mouse tumors compare to control. However, EPA treatment was associated with decreased plasma CCL2 levels compared with controls (P=0.04). Reduction in plasma CCL2 following EPA treatment predicted improved disease-free survival (HR 0.32; P=0.003). Lack of ‘CCL2 response’ was associated with a specific CRCLM gene expression signature. In conclusion, reduction in plasma CCL2 in patients with CRCLM treated with EPA predicts better clinical outcome and a specific tumor gene expression profile. Further work is needed to validate CCL2 as a therapeutic response biomarker for omega-3 fatty acid treatment of CRC patients. PMID:27058904

  14. Osteolytic lesions, cytogenetic features and bone marrow levels of cytokines and chemokines in multiple myeloma patients: Role of chemokine (C-C motif) ligand 20.

    Science.gov (United States)

    Palma, B Dalla; Guasco, D; Pedrazzoni, M; Bolzoni, M; Accardi, F; Costa, F; Sammarelli, G; Craviotto, L; De Filippo, M; Ruffini, L; Omedè, P; Ria, R; Aversa, F; Giuliani, N

    2016-02-01

    The relationship between bone marrow (BM) cytokine and chemokine levels, cytogenetic profiles and skeletal involvement in multiple myeloma (MM) patients is not yet defined. This study investigated a cohort of 455 patients including monoclonal gammopathy of uncertain significance (MGUS), smoldering MM and symptomatic MM patients. Skeletal surveys, positron emission tomography (PET)/computerized tomography (CT) and magnetic resonance imaging (MRI) were used to identify myeloma bone disease. Significantly higher median BM levels of both C-C motif Ligand (CCL)3 and CCL20 were found in MM patients with radiographic evidence of osteolytic lesions as compared with those without, and in all MM patients with positive PET/CT scans. BM levels of CCL3, CCL20, Activin-A and Dickkopf-1 (DKK-1) were significantly higher in patients with high bone disease as compared with patients with low bone disease. Moreover, CCL20 BM levels were significant predictors of osteolysis on X-rays by multivariate logistic analysis. On the other hand, DKK-1 levels were related to the presence of MRI lesions independently of the osteolysis at the X-rays. Our data define the relationship between bone disease and the BM cytokine and chemokine patterns highlighting the tight relationship between CCL20 BM levels and osteolysis in MM. PMID:26419509

  15. Preliminary study on serum paraoxonase-1 status and chemokine (C-C motif) ligand 2 in hospitalized elderly patients with catheter-associated asymptomatic bacteriuria.

    Science.gov (United States)

    Iftimie, S; García-Heredia, A; Pujol, I; Ballester, F; Fort-Gallifa, I; Simó, J M; Joven, J; Camps, J; Castro, A

    2016-09-01

    Urinary tract infections (UTI) are common among elderly patients in residential care facilities, as well as in the hospital setting. Identifying new biochemical markers of UTI is an active line of research since UTI management is resource intensive. Paraoxonase-1 (PON1) forms part of the patient's immune system, the response-to-injury and inflammation. Our study sought to evaluate alterations in inflammation-related paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2) in patients with an indwelling catheter to assess their potential usefulness as biomarkers of infection. Patients (n = 142) who had had the urinary catheter removed and 100 healthy volunteers were recruited. In all participants we measured serum PON1 activity, PON1 concentration, CCL2, procalcitonin and C-reactive protein (CRP). Results indicated that patients had higher CCL2, CRP and procalcitonin concentrations than the control group, and lower paraoxonase activity. There were no significant differences in PON1 concentrations. When comparing the diagnostic accuracy of CRP, procalcitonin, CCL2 and the PON1-related variables in discriminating between patients with and those without UTI, we found a considerable degree of overlap between groups, i.e., a low diagnostic accuracy. However, there were significant inverse logarithmic correlations between serum paraoxonase activity and the number of days the urinary catheter had been in situ. Our results suggest that measurement of these biochemical variables may be useful in investigating complications of long-term use of these devices and help to improve the economic and clinical investment required in the management of the often-associated infection. PMID:27334497

  16. Coregulator control of androgen receptor action by a novel nuclear receptor-binding motif.

    Science.gov (United States)

    Jehle, Katja; Cato, Laura; Neeb, Antje; Muhle-Goll, Claudia; Jung, Nicole; Smith, Emmanuel W; Buzon, Victor; Carbó, Laia R; Estébanez-Perpiñá, Eva; Schmitz, Katja; Fruk, Ljiljana; Luy, Burkhard; Chen, Yu; Cox, Marc B; Bräse, Stefan; Brown, Myles; Cato, Andrew C B

    2014-03-28

    The androgen receptor (AR) is a ligand-activated transcription factor that is essential for prostate cancer development. It is activated by androgens through its ligand-binding domain (LBD), which consists predominantly of 11 α-helices. Upon ligand binding, the last helix is reorganized to an agonist conformation termed activator function-2 (AF-2) for coactivator binding. Several coactivators bind to the AF-2 pocket through conserved LXXLL or FXXLF sequences to enhance the activity of the receptor. Recently, a small compound-binding surface adjacent to AF-2 has been identified as an allosteric modulator of the AF-2 activity and is termed binding function-3 (BF-3). However, the role of BF-3 in vivo is currently unknown, and little is understood about what proteins can bind to it. Here we demonstrate that a duplicated GARRPR motif at the N terminus of the cochaperone Bag-1L functions through the BF-3 pocket. These findings are supported by the fact that a selective BF-3 inhibitor or mutations within the BF-3 pocket abolish the interaction between the GARRPR motif(s) and the BF-3. Conversely, amino acid exchanges in the two GARRPR motifs of Bag-1L can impair the interaction between Bag-1L and AR without altering the ability of Bag-1L to bind to chromatin. Furthermore, the mutant Bag-1L increases androgen-dependent activation of a subset of AR targets in a genome-wide transcriptome analysis, demonstrating a repressive function of the GARRPR/BF-3 interaction. We have therefore identified GARRPR as a novel BF-3 regulatory sequence important for fine-tuning the activity of the AR.

  17. FTZ-Factor1 and Fushi tarazu interact via conserved nuclear receptor and coactivator motifs

    OpenAIRE

    Schwartz, Carol J.E.; Sampson, Heidi M.; Hlousek, Daniela; Percival-Smith, Anthony; Copeland, John W.R.; Simmonds, Andrew J.; Krause, Henry M.

    2001-01-01

    To activate transcription, most nuclear receptor proteins require coactivators that bind to their ligand-binding domains (LBDs). The Drosophila FTZ-Factor1 (FTZ-F1) protein is a conserved member of the nuclear receptor superfamily, but was previously thought to lack an AF2 motif, a motif that is required for ligand and coactivator binding. Here we show that FTZ-F1 does have an AF2 motif and that it is required to bind a coactivator, the homeodomain-containing protein Fushi tarazu (FTZ). We al...

  18. Cloning and functional characterization of the rabbit C-C chemokine receptor 2

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    Hamdouchi Chafiq

    2005-07-01

    Full Text Available Abstract Background CC-family chemokine receptor 2 (CCR2 is implicated in the trafficking of blood-borne monocytes to sites of inflammation and is implicated in the pathogenesis of several inflammatory diseases such as rheumatoid arthritis, multiple sclerosis and atherosclerosis. The major challenge in the development of small molecule chemokine receptor antagonists is the lack of cross-species activity to the receptor in the preclinical species. Rabbit models have been widely used to study the role of various inflammatory molecules in the development of inflammatory processes. Therefore, in this study, we report the cloning and characterization of rabbit CCR2. Data regarding the activity of the CCR2 antagonist will provide valuable tools to perform toxicology and efficacy studies in the rabbit model. Results Sequence alignment indicated that rabbit CCR2 shares 80 % identity to human CCR2b. Tissue distribution indicated that rabbit CCR2 is abundantly expressed in spleen and lung. Recombinant rabbit CCR2 expressed as stable transfectants in U-937 cells binds radiolabeled 125I-mouse JE (murine MCP-1 with a calculated Kd of 0.1 nM. In competition binding assays, binding of radiolabeled mouse JE to rabbit CCR2 is differentially competed by human MCP-1, -2, -3 and -4, but not by RANTES, MIP-1α or MIP-1β. U-937/rabbit CCR2 stable transfectants undergo chemotaxis in response to both human MCP-1 and mouse JE with potencies comparable to those reported for human CCR2b. Finally, TAK-779, a dual CCR2/CCR5 antagonist effectively inhibits the binding of 125I-mouse JE (IC50 = 2.3 nM to rabbit CCR2 and effectively blocks CCR2-mediated chemotaxis. Conclusion In this study, we report the cloning of rabbit CCR2 and demonstrate that this receptor is a functional chemotactic receptor for MCP-1.

  19. Endocytosis and Trafficking of Natriuretic Peptide Receptor-A: Potential Role of Short Sequence Motifs

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    Kailash N. Pandey

    2015-07-01

    Full Text Available The targeted endocytosis and redistribution of transmembrane receptors among membrane-bound subcellular organelles are vital for their correct signaling and physiological functions. Membrane receptors committed for internalization and trafficking pathways are sorted into coated vesicles. Cardiac hormones, atrial and brain natriuretic peptides (ANP and BNP bind to guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA and elicit the generation of intracellular second messenger cyclic guanosine 3',5'-monophosphate (cGMP, which lowers blood pressure and incidence of heart failure. After ligand binding, the receptor is rapidly internalized, sequestrated, and redistributed into intracellular locations. Thus, NPRA is considered a dynamic cellular macromolecule that traverses different subcellular locations through its lifetime. The utilization of pharmacologic and molecular perturbants has helped in delineating the pathways of endocytosis, trafficking, down-regulation, and degradation of membrane receptors in intact cells. This review describes the investigation of the mechanisms of internalization, trafficking, and redistribution of NPRA compared with other cell surface receptors from the plasma membrane into the cell interior. The roles of different short-signal peptide sequence motifs in the internalization and trafficking of other membrane receptors have been briefly reviewed and their potential significance in the internalization and trafficking of NPRA is discussed.

  20. Coregulator Control of Androgen Receptor Action by a Novel Nuclear Receptor-Binding Motif

    OpenAIRE

    Jehle, Katja; Cato, Laura; Neeb, Antje; Muhle-Goll, Claudia; Jung, Nicole; Smith, Emmanuel W.; Buzon, Victor; Carbó, Laia R.; Estébanez-Perpiñá, Eva; Schmitz, Katja; Fruk, Ljiljana; Luy, Burkhard; Chen, Yu; Cox, Marc B.; Bräse, Stefan

    2014-01-01

    The androgen receptor (AR) is a ligand-activated transcription factor that is essential for prostate cancer development. It is activated by androgens through its ligand-binding domain (LBD), which consists predominantly of 11 α-helices. Upon ligand binding, the last helix is reorganized to an agonist conformation termed activator function-2 (AF-2) for coactivator binding. Several coactivators bind to the AF-2 pocket through conserved LXXLL or FXXLF sequences to enhance the activity of the rec...

  1. Predicting kinase activity in angiotensin receptor phosphoproteomes based on sequence-motifs and interactions.

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    Rikke Bøgebo

    Full Text Available Recent progress in the understanding of seven-transmembrane receptor (7TMR signalling has promoted the development of a new generation of pathway selective ligands. The angiotensin II type I receptor (AT1aR is one of the most studied 7TMRs with respect to selective activation of the β-arrestin dependent signalling. Two complimentary global phosphoproteomics studies have analyzed the complex signalling induced by the AT1aR. Here we integrate the data sets from these studies and perform a joint analysis using a novel method for prediction of differential kinase activity from phosphoproteomics data. The method builds upon NetworKIN, which applies sophisticated linear motif analysis in combination with contextual network modelling to predict kinase-substrate associations with high accuracy and sensitivity. These predictions form the basis for subsequently nonparametric statistical analysis to identify likely activated kinases. This suggested that AT1aR-dependent signalling activates 48 of the 285 kinases detected in HEK293 cells. Of these, Aurora B, CLK3 and PKG1 have not previously been described in the pathway whereas others, such as PKA, PKB and PKC, are well known. In summary, we have developed a new method for kinase-centric analysis of phosphoproteomes to pinpoint differential kinase activity in large-scale data sets.

  2. HIV-1 Nef down-modulates C-C and C-X-C chemokine receptors via ubiquitin and ubiquitin-independent mechanism.

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    Prabha Chandrasekaran

    Full Text Available Human and Simian Immunodeficiency virus (HIV-1, HIV-2, and SIV encode an accessory protein, Nef, which is a pathogenesis and virulence factor. Nef is a multivalent adapter that dysregulates the trafficking of many immune cell receptors, including chemokine receptors (CKRs. Physiological endocytic itinerary of agonist occupied CXCR4 involves ubiquitinylation of the phosphorylated receptor at three critical lysine residues and dynamin-dependent trafficking through the ESCRT pathway into lysosomes for degradation. Likewise, Nef induced CXCR4 degradation was critically dependent on the three lysines in the C-terminal -SSLKILSKGK- motif. Nef directly recruits the HECT domain E3 ligases AIP4 or NEDD4 to CXCR4 in the resting state. This mechanism was confirmed by ternary interactions of Nef, CXCR4 and AIP4 or NEDD4; by reversal of Nef effect by expression of catalytically inactive AIP4-C830A mutant; and siRNA knockdown of AIP4, NEDD4 or some ESCRT-0 adapters. However, ubiquitinylation dependent lysosomal degradation was not the only mechanism by which Nef downregulated CKRs. Agonist and Nef mediated CXCR2 (and CXCR1 degradation was ubiquitinylation independent. Nef also profoundly downregulated the naturally truncated CXCR4 associated with WHIM syndrome and engineered variants of CXCR4 that resist CXCL12 induced internalization via an ubiquitinylation independent mechanism.

  3. Leucine-based receptor sorting motifs are dependent on the spacing relative to the plasma membrane

    DEFF Research Database (Denmark)

    Geisler, C; Dietrich, J; Nielsen, B L;

    1998-01-01

    amino acid, is constitutively active. In this study, we have investigated how the spacing relative to the plasma membrane affects the function of both types of leucine-based motifs. For phosphorylation-dependent leucine-based motifs, a minimal spacing of 7 residues between the plasma membrane and the...... phospho-acceptor was required for phosphorylation and thereby activation of the motifs. For constitutively active leucine-based motifs, a minimal spacing of 6 residues between the plasma membrane and the acidic residue was required for optimal activity of the motifs. In addition, we found that the acidic......Many integral membrane proteins contain leucine-based motifs within their cytoplasmic domains that mediate internalization and intracellular sorting. Two types of leucine-based motifs have been identified. One type is dependent on phosphorylation, whereas the other type, which includes an acidic...

  4. Putative bioactive motif of tritrpticin revealed by an antibody with biological receptor-like properties.

    Directory of Open Access Journals (Sweden)

    Raghava Sharma

    Full Text Available Antimicrobial peptides represent one of the most promising future strategies for combating infections and microbial drug resistance. Tritrpticin is a 13mer tryptophan-rich cationic antimicrobial peptide with a broad spectrum of activity whose application in antimicrobial therapy has been hampered by ambiguity about its biological target and consequently the molecular interactions necessary for its antimicrobial activity. The present study provides clues about the mechanism of action of tritripticin by using a unique monoclonal antibody (mAb as a 'physiological' structural scaffold. A pool of mAbs were generated against tritrpticin and based on its high affinity and ability to bind tritrpticin analogs, mAb 6C6D7 was selected and characterized further. In a screening of phage displayed random peptides, this antibody was able to identify a novel antimicrobial peptide with low sequence homology to tritrpticin, suggesting that the mAb possessed the physico-chemical characteristics mimicking the natural receptor. Subsequently, thermodynamics and molecular modeling identified a core group of hydrophobic residues in tritrpticin arranged in a distorted's' shaped conformation as critical for antibody binding. Comparison of the mAb induced conformation with the micelle bound structure of tritrpticin reveals how a common motif may be able to interact with multiple classes of biomolecules thus extending the target range of this innate immune peptide. Based on the concurrence between thermodynamic and structural data our results reveal a template that can be used to design novel antimicrobial pharmacophores while simultaneously demonstrating at a more fundamental level the potential of mAbs to act as receptor surrogates.

  5. Down-regulation of the alpha-2C adrenergic receptor: involvement of a serine/threonine motif in the third cytoplasmic loop

    OpenAIRE

    Deupree, Jean D; Borgeson, Claudia D.; Bylund, David B.

    2002-01-01

    Background The mechanisms by which alpha-2 adrenergic receptors are down-regulated following chronic exposure to agonist are not well understood. Interestingly, the human alpha-2C receptor does not down-regulate, whereas the opossum alpha-2C receptor does down-regulate. A comparison of the amino acid sequence of the third intracellular loop of these two receptors shows that the opossum alpha-2C receptor contains a potential G protein-coupled receptor kinase (GRK)phosphorylation motif (EESSTSE...

  6. Comparative analysis of evolutionarily conserved motifs of epidermal growth factor receptor 2 (HER2 predicts novel potential therapeutic epitopes.

    Directory of Open Access Journals (Sweden)

    Xiaohong Deng

    Full Text Available Overexpression of human epidermal growth factor receptor 2 (HER2 is associated with tumor aggressiveness and poor prognosis in breast cancer. With the availability of therapeutic antibodies against HER2, great strides have been made in the clinical management of HER2 overexpressing breast cancer. However, de novo and acquired resistance to these antibodies presents a serious limitation to successful HER2 targeting treatment. The identification of novel epitopes of HER2 that can be used for functional/region-specific blockade could represent a central step in the development of new clinically relevant anti-HER2 antibodies. In the present study, we present a novel computational approach as an auxiliary tool for identification of novel HER2 epitopes. We hypothesized that the structurally and linearly evolutionarily conserved motifs of the extracellular domain of HER2 (ECD HER2 contain potential druggable epitopes/targets. We employed the PROSITE Scan to detect structurally conserved motifs and PRINTS to search for linearly conserved motifs of ECD HER2. We found that the epitopes recognized by trastuzumab and pertuzumab are located in the predicted conserved motifs of ECD HER2, supporting our initial hypothesis. Considering that structurally and linearly conserved motifs can provide functional specific configurations, we propose that by comparing the two types of conserved motifs, additional druggable epitopes/targets in the ECD HER2 protein can be identified, which can be further modified for potential therapeutic application. Thus, this novel computational process for predicting or searching for potential epitopes or key target sites may contribute to epitope-based vaccine and function-selected drug design, especially when x-ray crystal structure protein data is not available.

  7. Cis and trans regulatory mechanisms control AP2-mediated B cell receptor endocytosis via select tyrosine-based motifs.

    Directory of Open Access Journals (Sweden)

    Kathleen Busman-Sahay

    Full Text Available Following antigen recognition, B cell receptor (BCR-mediated endocytosis is the first step of antigen processing and presentation to CD4+ T cells, a crucial component of the initiation and control of the humoral immune response. Despite this, the molecular mechanism of BCR internalization is poorly understood. Recently, studies of activated B cell-like diffuse large B cell lymphoma (ABC DLBCL have shown that mutations within the BCR subunit CD79b leads to increased BCR surface expression, suggesting that CD79b may control BCR internalization. Adaptor protein 2 (AP2 is the major mediator of receptor endocytosis via clathrin-coated pits. The BCR contains five putative AP2-binding YxxØ motifs, including four that are present within two immunoreceptor tyrosine-based activation motifs (ITAMs. Using a combination of in vitro and in situ approaches, we establish that the sole mediator of AP2-dependent BCR internalization is the membrane proximal ITAM YxxØ motif in CD79b, which is a major target of mutation in ABC DLBCL. In addition, we establish that BCR internalization can be regulated at a minimum of two different levels: regulation of YxxØ AP2 binding in cis by downstream ITAM-embedded DCSM and QTAT regulatory elements and regulation in trans by the partner cytoplasmic domain of the CD79 heterodimer. Beyond establishing the basic rules governing BCR internalization, these results illustrate an underappreciated role for ITAM residues in controlling clathrin-dependent endocytosis and highlight the complex mechanisms that control the activity of AP2 binding motifs in this receptor system.

  8. Proinsulin Shares a Motif with Interleukin-1α (IL-1α) and Induces Inflammatory Cytokine via Interleukin-1 Receptor 1*

    Science.gov (United States)

    Lee, Siyoung; Kim, Eunsom; Jhun, Hyunjhung; Hong, Jaewoo; Kwak, Areum; Jo, Seunghyun; Bae, Suyoung; Lee, Jongho; Kim, Busun; Lee, Jungmin; Youn, Sulah; Kim, Somi; Kim, Miyeon; Kim, Hyunwoo; Lee, Youngmin; Choi, Dong-Ki; Kim, Yong-Sung; Kim, Soohyun

    2016-01-01

    Although it has been established that diabetes increases susceptibility to infections, the role of insulin (INS) in the immune response is unknown. Here, we investigated the immunological function of INS. Proinsulin dimer (pINSd) was a potent immune stimulus that induced inflammatory cytokines, but mature INS was unable to induce an immune response. An affinity-purified rabbit polyclonal antibody raised against mature IL-1α recognized IL-1α and pINS but failed to detect mature INS and IL-1β. Analysis of the pINS sequence revealed the existence of an INS/IL-1α motif in the C-peptide of pINS. Surprisingly, the INS/IL-1α motif was recognized by monoclonal antibody raised against IL-1α. Deleting the INS/IL-1α motif in pINSd and IL-1α changed their activities. To investigate the pINSd receptor, the reconstitution of IL-1 receptor 1 (IL-1R1) in Wish cells restored pINSd activity that was reversed by an IL-1R antagonist. These data suggested that pINSd needs IL-1R1 for inflammatory cytokine induction. Mouse embryo fibroblast cells of IL-1R1-deficient mice further confirmed that pINSd promotes immune responses through IL-1R1. PMID:27226621

  9. Proinsulin Shares a Motif with Interleukin-1α (IL-1α) and Induces Inflammatory Cytokine via Interleukin-1 Receptor 1.

    Science.gov (United States)

    Lee, Siyoung; Kim, Eunsom; Jhun, Hyunjhung; Hong, Jaewoo; Kwak, Areum; Jo, Seunghyun; Bae, Suyoung; Lee, Jongho; Kim, Busun; Lee, Jungmin; Youn, Sulah; Kim, Somi; Kim, Miyeon; Kim, Hyunwoo; Lee, Youngmin; Choi, Dong-Ki; Kim, Yong-Sung; Kim, Soohyun

    2016-07-01

    Although it has been established that diabetes increases susceptibility to infections, the role of insulin (INS) in the immune response is unknown. Here, we investigated the immunological function of INS. Proinsulin dimer (pINSd) was a potent immune stimulus that induced inflammatory cytokines, but mature INS was unable to induce an immune response. An affinity-purified rabbit polyclonal antibody raised against mature IL-1α recognized IL-1α and pINS but failed to detect mature INS and IL-1β. Analysis of the pINS sequence revealed the existence of an INS/IL-1α motif in the C-peptide of pINS. Surprisingly, the INS/IL-1α motif was recognized by monoclonal antibody raised against IL-1α. Deleting the INS/IL-1α motif in pINSd and IL-1α changed their activities. To investigate the pINSd receptor, the reconstitution of IL-1 receptor 1 (IL-1R1) in Wish cells restored pINSd activity that was reversed by an IL-1R antagonist. These data suggested that pINSd needs IL-1R1 for inflammatory cytokine induction. Mouse embryo fibroblast cells of IL-1R1-deficient mice further confirmed that pINSd promotes immune responses through IL-1R1. PMID:27226621

  10. C-C chemokine receptor 2 inhibitor ameliorates hepatic steatosis by improving ER stress and inflammation in a type 2 diabetic mouse model.

    Directory of Open Access Journals (Sweden)

    Hong-Min Kim

    Full Text Available Hepatic steatosis is the accumulation of excess fat in the liver. Recently, hepatic steatosis has become more important because it occurs in the patients with obesity, type 2 diabetes, and hyperlipidemia and is associated with endoplasmic reticulum (ER stress and insulin resistance. C-C chemokine receptor 2 (CCR2 inhibitor has been reported to improve inflammation and glucose intolerance in diabetes, but its mechanisms remained unknown in hepatic steatosis. We examined whether CCR2 inhibitor improves ER stress-induced hepatic steatosis in type 2 diabetic mice. In this study, db/db and db/m (n = 9 mice were fed CCR2 inhibitor (2 mg/kg/day for 9 weeks. In diabetic mice, CCR2 inhibitor decreased plasma and hepatic triglycerides levels and improved insulin sensitivity. Moreover, CCR2 inhibitor treatment decreased ER stress markers (e.g., BiP, ATF4, CHOP, and XBP-1 and inflammatory cytokines (e.g., TNFα, IL-6, and MCP-1 while increasing markers of mitochondrial biogenesis (e.g., PGC-1α, Tfam, and COX1 in the liver. We suggest that CCR2 inhibitor may ameliorate hepatic steatosis by reducing ER stress and inflammation in type 2 diabetes mellitus.

  11. High constitutive activity of a virus-encoded seven transmembrane receptor in the absence of the conserved DRY motif (Asp-Arg-Tyr) in transmembrane helix 3

    DEFF Research Database (Denmark)

    Rosenkilde, Mette M; Kledal, Thomas N; Schwartz, Thue W

    2005-01-01

    The highly conserved Arg in the so-called DRY motif (Asp-Arg-Tyr) at the intracellular end of transmembrane helix 3 is in general considered as an essential residue for G protein coupling in rhodopsin-like seven transmembrane (7TM) receptors. In the open reading frame 74 (ORF74) receptor encoded by...

  12. Palmitoylation of protease-activated receptor-1 regulates adaptor protein complex-2 and -3 interaction with tyrosine-based motifs and endocytic sorting.

    Science.gov (United States)

    Canto, Isabel; Trejo, JoAnn

    2013-05-31

    Protease-activated receptor-1 (PAR1) is a G protein-coupled receptor for the coagulant protease thrombin. Thrombin binds to and cleaves the N terminus of PAR1, generating a new N terminus that functions as a tethered ligand that cannot diffuse away. In addition to rapid desensitization, PAR1 trafficking is critical for the regulation of cellular responses. PAR1 displays constitutive and agonist-induced internalization. Constitutive internalization of unactivated PAR1 is mediated by the clathrin adaptor protein complex-2 (AP-2), which binds to a distal tyrosine-based motif localized within the C-terminal tail (C-tail) domain. Once internalized, PAR1 is sorted from endosomes to lysosomes via AP-3 interaction with a second C-tail tyrosine motif proximal to the transmembrane domain. However, the regulatory processes that control adaptor protein recognition of PAR1 C-tail tyrosine-based motifs are not known. Here, we report that palmitoylation of PAR1 is critical for regulating proper utilization of tyrosine-based motifs and endocytic sorting. We show that PAR1 is basally palmitoylated at highly conserved C-tail cysteines. A palmitoylation-deficient PAR1 mutant is competent to signal and exhibits a marked increase in constitutive internalization and lysosomal degradation compared with wild type receptor. Intriguingly, enhanced constitutive internalization of PAR1 is mediated by AP-2 and requires the proximal tyrosine-based motif rather than the distal tyrosine motif used by wild type receptor. Moreover, palmitoylation-deficient PAR1 displays increased degradation that is mediated by AP-3. These findings suggest that palmitoylation of PAR1 regulates appropriate utilization of tyrosine-based motifs by adaptor proteins and endocytic trafficking, processes that are critical for maintaining appropriate expression of PAR1 at the cell surface. PMID:23580642

  13. T cell receptor zeta allows stable expression of receptors containing the CD3gamma leucine-based receptor-sorting motif

    DEFF Research Database (Denmark)

    Dietrich, J; Geisler, C

    1998-01-01

    that the leucine-based motif in these complexes was inactive. In contrast, the CD4/CD3gamma chimeras did not associate with TCRzeta, and the leucine-based motif in these chimeras was constitutively active resulting in a high spontaneous internalization rate and low expression of the chimeras at the cell surface...

  14. A systematic scan of interactions with tyrosine motifs in the erythropoietin receptor using a mammalian 2-hybrid approach.

    Science.gov (United States)

    Montoye, Tony; Lemmens, Irma; Catteeuw, Dominiek; Eyckerman, Sven; Tavernier, Jan

    2005-06-01

    Signaling via the erythropoietin receptor (EpoR) depends on the interaction of several proteins with phosphorylated tyrosine-containing motifs in its cytosolic domain. Detailed mapping of these interactions is required for an accurate insight into Epo signaling. We recently developed a mammalian protein-protein interaction trap (MAPPIT), a cytokine receptor-based 2-hybrid method that operates in intact Hek293-T mammalian cells. As baits, we used intracellular segments of the EpoR containing 1 or 2 tyrosines. Several known signaling molecules, including cytokine-inducible SH2-containing protein (CIS), suppressor of cytokine signaling-2 (SOCS2), phosphatidylinositol 3'-kinase (PI3-K), phospholipase C-gamma (PLC-gamma), and signal transducer and activator of transcription 5 (STAT5) were used as prey. We also extended the MAPPIT method to enable interaction analysis with wild-type EpoR. In this relay MAPPIT approach, instead of using isolated EpoR fragments as bait, we used the full-length EpoR itself as a "receptor bait." Finally, we introduced MAPPIT in the erythroleukemic TF-1 cell line, which is a more natural setting of the EpoR. With these strategies several known interactions with the EpoR were analyzed and evidence for new interactions was obtained. PMID:15644415

  15. Bacteria binding by DMBT1/SAG/gp-340 is confined to the VEVLXXXXW motif in its scavenger receptor cysteine-rich domains

    DEFF Research Database (Denmark)

    Bikker, Floris J; Ligtenberg, Antoon J M; End, Caroline;

    2004-01-01

    synthetic peptides covering the SRCR consensus sequence to identify a 16-amino acid bacteria-binding protein loop (peptide SRCRP2; QGRVEVLYRGSWGTVC) within the SRCR domains. In this study, using overlapping peptides, we pinpointed the minimal bacteria-binding site on SRCRP2, and thus DMBT1, to an 11-amino...... acid motif (DMBT1 pathogen-binding site 1 or DMBT1pbs1; GRVEVLYRGSW). An alanine substitution scan revealed that VEVL and Trp are critical residues in this motif. Bacteria binding by DMBT1pbs1 was different from the bacteria binding by the macrophage receptor MARCO in which an RXR motif was critical....... In addition, the homologous consensus sequences of a number of SRCR proteins were synthesized and tested for bacteria binding. Only consensus sequences of DMBT1 orthologues bound bacteria by this motif....

  16. Protein kinase A regulation of P2X(4) receptors: requirement for a specific motif in the C-terminus.

    Science.gov (United States)

    Brown, David A; Yule, David I

    2010-02-01

    The P2X purinergic receptor sub-family of ligand-gated ion channels are subject to protein kinase modulation. We have previously demonstrated that P2X(4)R signaling can be positively regulated by increasing intracellular cAMP levels. The molecular mechanism underlying this effect was, however, unknown. The present study initially addressed whether protein kinase A (PKA) activation was required. Subsequently a mutational approach was utilized to determine which region of the receptor was required for this potentiation. In both DT-40 3KO and HEK-293 cells transiently expressing P2X(4)R, forskolin treatment enhanced ATP-mediated signaling. Specific PKA inhibitors prevented the forskolin-induced enhancement of ATP-mediated inward currents in P2X(4)R expressing HEK-293 cells. To define which region of the P2X(4)R was required for the potentiation, mutations were generated in the cytoplasmic C-terminal tail. It was determined that a limited region of the C-terminus, consisting of a non-canonical tyrosine based sorting motif, was required for the effects of PKA. Of note, this region does not harbor any recognizable PKA phosphorylation motifs, and no direct phosphorylation of P2X(4)R was detected, suggesting that PKA phosphorylation of an accessory protein interacts with the endocytosis motif in the C-terminus of the P2X(4)R. In support of this notion, using Total Internal Reflection Fluorescence Microscopy (TIRF)\\ P2X(4)-EGFP was shown to accumulate at/near the plasma membrane following forskolin treatment. In addition, disrupting the endocytosis machinery using a dominant-negative dynamin construct also prevented the PKA-mediated enhancement of ATP-stimulated Ca(2+) signals. Our results are consistent with a novel mechanism of P2XR regulation, whereby PKA activity, without directly phosphorylating P2X(4)R, markedly enhances ATP-stimulated P2X(4)R currents and hence cytosolic Ca(2+) signals. This may occur at least in part, by altering the trafficking of a population of

  17. Receptor activation and 2 distinct COOH-terminal motifs control G-CSF receptor distribution and internalization kinetics

    NARCIS (Netherlands)

    L.H.J. Aarts (Bart); O. Roovers (Onno); A.C. Ward (Alister); I.P. Touw (Ivo)

    2004-01-01

    textabstractWe have studied the intracellular distribution and internalization kinetics of the granulocyte colony-stimulating factor receptor (G-CSF-R) in living cells using fusion constructs of wild-type or mutant G-CSF-R and enhanced green fluorescent protein (EGFP). Under steady

  18. Identifying the activation motif in the N-terminal of rainbow trout and zebrafish melanocortin-2 receptor accessory protein 1 (MRAP1) orthologs.

    Science.gov (United States)

    Dores, Robert M; Liang, Liang; Hollmann, Rebecca E; Sandhu, Navdeep; Vijayan, Mathilakath M

    2016-08-01

    The activation of mammalian melanocortin-2 receptor (MC2R) orthologs is dependent on a four-amino acid activation motif (LDYL/I) located in the N-terminal of mammalian MRAP1 (melanocortin-2 receptor accessory protein). Previous alanine substitution analysis had shown that the Y residue in this motif appears to be the most important for mediating the activation of mammalian MC2R orthologs. Similar, but not identical amino acid motifs were detected in rainbow trout MRAP1 (YDYL) and zebrafish MRAP1 (YDYV). To determine the importance of these residues in the putative activation motifs, rainbow trout and zebrafish MRAP1 orthologs were individually co-expressed in CHO cells with rainbow trout MC2R, and the activation of this receptor with either the wild-type MRAP1 ortholog or alanine-substituted analogs of the two teleost MRAP1s was analyzed. Alanine substitutions at all four amino acid positions in rainbow trout MRAP1 blocked activation of the rainbow trout MC2R. Single alanine substitutions of the D and Y residues in rainbow trout and zebrafish MRAP1 indicate that these two residues play a significant role in the activation of rainbow trout MC2R. These observations indicate that there are subtle differences in the way that teleost and mammalian MRAPs are involved in the activation of their corresponding MC2R orthologs. PMID:26752246

  19. Corticotropin-Releasing Hormone Receptor Type 1 (CRHR1 Clustering with MAGUKs Is Mediated via Its C-Terminal PDZ Binding Motif.

    Directory of Open Access Journals (Sweden)

    Julia Bender

    Full Text Available The corticotropin-releasing hormone receptor type 1 (CRHR1 plays an important role in orchestrating neuroendocrine, behavioral, and autonomic responses to stress. To identify molecules capable of directly modulating CRHR1 signaling, we performed a yeast-two-hybrid screen using the C-terminal intracellular tail of the receptor as bait. We identified several members of the membrane-associated guanylate kinase (MAGUK family: postsynaptic density protein 95 (PSD95, synapse-associated protein 97 (SAP97, SAP102 and membrane associated guanylate kinase, WW and PDZ domain containing 2 (MAGI2. CRHR1 is co-expressed with the identified MAGUKs and with the additionally investigated PSD93 in neurons of the adult mouse brain and in primary hippocampal neurons, supporting the probability of a physiological interaction in vivo. The C-terminal PDZ (PSD-95, discs large, zona occludens 1 binding motif of CRHR1 is essential for its physical interaction with MAGUKs, as revealed by the CRHR1-STAVA mutant, which harbors a functionally impaired PDZ binding motif. The imitation of a phosphorylation at Thr413 within the PDZ binding motif also disrupted the interaction with MAGUKs. In contrast, distinct PDZ domains within the identified MAGUKs are involved in the interactions. Expression of CRHR1 in primary neurons demonstrated its localization throughout the neuronal plasma membrane, including the excitatory post synapse, where the receptor co-localized with PSD95 and SAP97. The co-expression of CRHR1 and respective interacting MAGUKs in HEK293 cells resulted in a clustered subcellular co-localization which required an intact PDZ binding motif. In conclusion, our study characterized the PDZ binding motif-mediated interaction of CRHR1 with multiple MAGUKs, which directly affects receptor function.

  20. Getting from A to B-exploring the activation motifs of the class B adhesion G protein-coupled receptor subfamily G member 4/GPR112

    DEFF Research Database (Denmark)

    Peeters, Miriam C; Mos, Iris; Lenselink, Eelke B;

    2016-01-01

    The adhesion G protein-coupled receptors (ADGRs/class B2 G protein-coupled receptors) constitute an ancient family of G protein-coupled receptors that have recently been demonstrated to play important roles in cellular and developmental processes. Here, we describe a first insight...... into the structure-function relationship of ADGRs using the family member ADGR subfamily G member 4 (ADGRG4)/GPR112 as a model receptor. In a bioinformatics approach, we compared conserved, functional elements of the well-characterized class A and class B1 secretin-like G protein-coupled receptors with the ADGRs. We...... identified several potential equivalent motifs and subjected those to mutational analysis. The importance of the mutated residues was evaluated by examining their effect on the high constitutive activity of the N-terminally truncated ADGRG4/GPR112 in a 1-receptor-1-G protein Saccharomyces cerevisiae...

  1. Comparing Class A GPCRs to bitter taste receptors: Structural motifs, ligand interactions and agonist-to-antagonist ratios.

    Science.gov (United States)

    Di Pizio, Antonella; Levit, Anat; Slutzki, Michal; Behrens, Maik; Karaman, Rafik; Niv, Masha Y

    2016-01-01

    G protein-coupled receptors (GPCRs) are seven transmembrane (TM) proteins that play a key role in human physiology. The GPCR superfamily comprises about 800 members, classified into several classes, with rhodopsin-like Class A being the largest and most studied thus far. A huge component of the human repertoire consists of the chemosensory GPCRs, including ∼400 odorant receptors, 25 bitter taste receptors (TAS2Rs), which are thought to guard the organism from consuming poisons, and sweet and umami TAS1R heteromers, which indicate the nutritive value of food. The location of the binding site of TAS2Rs is similar to that of Class A GPCRs. However, most of the known bitter ligands are agonists, with only a few antagonists documented thus far. The agonist-to-antagonist ratios of Class A GPCRs vary, but in general are much lower than for TAS2Rs. For a set of well-studied GPCRs, a gradual change in agonists-to-antagonists ratios is observed when comparing low (10 μM)- and high (10 nM)-affinity ligand sets from ChEMBL and the DrugBank set of drugs. This shift reflects pharmaceutical bias toward the therapeutically desirable pharmacology for each of these GPCRs, while the 10 μM sets possibly represent the native tendency of the receptors toward either agonists or antagonists. Analyzing ligand-GPCR interactions in 56 X-ray structures representative of currently available structural data, we find that the N-terminus, TM1 and TM2 are more involved in binding of antagonists than of agonists. On the other hand, ECL2 tends to be more involved in binding of agonists. This is of interest, since TAS2Rs harbor variations on the typical Class A sequence motifs, including the absence of the ECL2-TM3 disulfide bridge. This suggests an alternative mode of regulation of conformational states for TAS2Rs, with potentially less stabilized inactive state. The comparison of TAS2Rs and Class A GPCRs structural features and the pharmacology of the their ligands highlights the intricacies of

  2. In vivo Regulation of the Allergic Response by the Interleukin 4 Receptor Alpha Chain Immunoreceptor Tyrosine-based Inhibitory Motif

    Science.gov (United States)

    Tachdjian, Raffi; Khatib, Shadi Al; Schwinglshackl, Andreas; Kim, Hong Sook; Chen, Andrew; Blasioli, Julie; Mathias, Clinton; Kim, Hye-Young; Umetsu, Dale T.; Oettgen, Hans C.; Chatila, Talal A.

    2010-01-01

    Background Signaling by IL-4 and IL-13 via the IL-4 receptor alpha chain (IL-4Rα) plays a critical role in the pathology of allergic diseases. The IL-4Rα is endowed with an immunoreceptor tyrosine-based inhibitory motif (ITIM), centered on tyrosine 709 (Y709) in the cytoplasmic domain, that binds a number of regulatory phosphatases. The function of the ITIM in the in vivo regulation of IL-4R signaling remains unknown. Objective To determine the in vivo function of the IL-4Rα ITIM using mice in which the ITIM was inactivated by mutagenesis of the tyrosine Y709 residue into phenylalanine (F709). Methods F709 ITIM mutant mice were derived by knockin mutagenesis. Activation of intracellular signaling cascades by IL-4 and IL-13 was assessed by intracellular staining of phosphorylated signaling intermediates and by gene expression analysis. In vivo responses to allergic sensitization were assessed using models of allergic airway inflammation. Results The F709 mutation increased STAT6 phosphorylation by IL-4 and, disproportionately, by IL-13. This was associated with exaggerated Th2 polarization, enhanced alternative macrophage activation by IL-13, augmented basal and antigen-induced IgE responses and intensified allergen-induced eosinophilic airway inflammation and hyperreactivity. Conclusions These results point to a physiologic negative regulatory role for the Y709 ITIM in signaling via IL-4Rα, especially by IL-13. PMID:20392476

  3. Comparative analysis of evolutionarily conserved motifs of epidermal growth factor receptor 2 (HER2) predicts novel potential therapeutic epitopes

    DEFF Research Database (Denmark)

    Deng, Xiaohong; Zheng, Xuxu; Yang, Huanming;

    2014-01-01

    druggable epitopes/targets. We employed the PROSITE Scan to detect structurally conserved motifs and PRINTS to search for linearly conserved motifs of ECD HER2. We found that the epitopes recognized by trastuzumab and pertuzumab are located in the predicted conserved motifs of ECD HER2, supporting our...... relevant anti-HER2 antibodies. In the present study, we present a novel computational approach as an auxiliary tool for identification of novel HER2 epitopes. We hypothesized that the structurally and linearly evolutionarily conserved motifs of the extracellular domain of HER2 (ECD HER2) contain potential...... initial hypothesis. Considering that structurally and linearly conserved motifs can provide functional specific configurations, we propose that by comparing the two types of conserved motifs, additional druggable epitopes/targets in the ECD HER2 protein can be identified, which can be further modified...

  4. Identification of the bioactive and consensus peptide motif from Momordica charantia insulin receptor-binding protein.

    Science.gov (United States)

    Lo, Hsin-Yi; Li, Chia-Cheng; Ho, Tin-Yun; Hsiang, Chien-Yun

    2016-08-01

    Many food bioactive peptides with diverse functions have been discovered by studying plant proteins. We have previously identified a 68-residue insulin receptor (IR)-binding protein (mcIRBP) from Momordica charantia that exhibits hypoglycemic effects in mice via interaction with IR. By in vitro digestion, we found that mcIRBP-19, spanning residues 50-68 of mcIRBP, enhanced the binding of insulin to IR, stimulated the phosphorylation of PDK1 and Akt, induced the expression of glucose transporter 4, and stimulated both the uptake of glucose in cells and the clearance of glucose in diabetic mice. Furthermore, mcIRBP-19 homologs were present in various plants and shared similar β-hairpin structures and IR kinase-activating abilities to mcIRBP-19. In conclusion, our findings suggested that mcIRBP-19 is a blood glucose-lowering bioactive peptide that exhibits IR-binding potentials. Moreover, we newly identified novel IR-binding bioactive peptides in various plants which belonged to different taxonomic families. PMID:26988505

  5. Site-specific labeling of the type 1 ryanodine receptor using biarsenical fluorophores targeted to engineered tetracysteine motifs.

    Directory of Open Access Journals (Sweden)

    James D Fessenden

    Full Text Available The type 1 ryanodine receptor (RyR1 is an intracellular Ca(2+ release channel that mediates skeletal muscle excitation contraction coupling. While the overall shape of RyR1 has been elucidated using cryo electron microscopic reconstructions, fine structural details remain elusive. To better understand the structure of RyR1, we have previously used a cell-based fluorescence resonance energy transfer (FRET method using a fused green fluorescent protein (GFP donor and a fluorescent acceptor, Cy3NTA that binds specifically to short poly-histidine 'tags' engineered into RyR1. However, the need to permeabilize cells to allow Cy3NTA entry as well as the noncovalent binding of Cy3NTA to the His tag limits future applications of this technique for studying conformational changes of the RyR. To overcome these problems, we used a dodecapeptide sequence containing a tetracysteine (Tc motif to target the biarsenical fluorophores, FlAsH and ReAsH to RyR1. These compounds freely cross intact cell membranes where they then bind covalently to the tetracysteine motif. First, we used this system to conduct FRET measurements in intact cells by fusing a yellow fluorescent protein (YFP FRET donor to the N-terminus of RyR1 and then targeting the FRET acceptor, ReAsH to an adjacent Tc tag. Moderate energy transfer (∼33% was observed whereas ReAsH incubation of a YFPRyR1 fusion protein lacking the Tc tag resulted in no detectable FRET. We also developed a FRET-based system that did not require RyR fluorescent protein fusions by labeling N-terminal Tc-tagged RyR1 with FlAsH, a FRET donor and then targeting the FRET acceptor Cy3NTA to an adjacent decahistidine (His10 tag. A high degree of energy transfer (∼66% indicated proper binding of both compounds to these unique recognition sequences in RyR1. Thus, these two systems should provide unprecedented flexibility in future FRET-based structural determinations of RyR1.

  6. On the Michael addition of water to C = C bonds

    NARCIS (Netherlands)

    Chen, B.

    2015-01-01

    β-Hydroxy carbonyl compounds are an important class of compounds often found as a common structural motif in natural products. Although the molecules themselves look rather simple, their synthesis can be challenging. Water addition to conjugated C = C bonds opens up a straightforward route for the p

  7. Comparative Study of C, C++, C# and Java Programming Languages

    OpenAIRE

    Chen, Hao

    2010-01-01

    With the rapid development of software industry, more and more people want to learn programming languages. But nowadays there are more than 200 programming languages available, only a few of them can be applied comparatively widely. In this thesis, the research in programming language was conducted. Four of the most popular programming languages C, C++, C# and Java are chosen to be the objects to study. The technical features of these four programming languages were summarized and compar...

  8. Consensus PP1 binding motifs regulate transcriptional corepression and alternative RNA splicing activities of the steroid receptor coregulators, p54nrb and PSF.

    Science.gov (United States)

    Liu, Liangliang; Xie, Ning; Rennie, Paul; Challis, John R G; Gleave, Martin; Lye, Stephen J; Dong, Xuesen

    2011-07-01

    Originally identified as essential pre-mRNA splicing factors, non-POU-domain-containing, octamer binding protein (p54nrb) and PTB-associated RNA splicing factor (PSF) are also steroid receptor corepressors. The mechanisms by which p54nrb and PSF regulate gene transcription remain unclear. Both p54nrb and PSF contain protein phosphatase 1 (PP1) consensus binding RVxF motifs, suggesting that PP1 may regulate phosphorylation status of p54nrb and PSF and thus their function in gene transcription. In this report, we demonstrated that PP1 forms a protein complex with both p54nrb and PSF. PP1 interacts directly with the RVxF motif only in p54nrb, but not in PSF. Association with PP1 results in dephosphorylation of both p54nrb and PSF in vivo and the loss of their transcriptional corepressor activities. Using the CD44 minigene as a reporter, we showed that PP1 regulates p54nrb and PSF alternative splicing activities that determine exon skipping vs. inclusion in the final mature RNA for translation. In addition, changes in transcriptional corepression and RNA splicing activities of p54nrb and PSF are correlated with alterations in protein interactions of p54nrb and PSF with transcriptional corepressors such as Sin3A and histone deacetylase 1, and RNA splicing factors such as U1A and U2AF. Furthermore, we demonstrated a novel function of the RVxF motif within PSF that enhances its corepression and RNA splicing activities independent of PP1. We conclude that the RVxF motifs play an important role in controlling the multifunctional properties of p54nrb and PSF in the regulation of gene transcription.

  9. CD3 gamma contains a phosphoserine-dependent di-leucine motif involved in down-regulation of the T cell receptor

    DEFF Research Database (Denmark)

    Dietrich, J; Hou, X; Wegener, A M;

    1994-01-01

    Several cell surface receptors including the T cell receptor (TCR) are phosphorylated and down-regulated following activation of protein kinase C (PKC). Among other substrates the activated PKC in T cells phosphorylates the CD3 gamma subunit of the TCR. To investigate the role of CD3 gamma...... phosphorylation in PKC-mediated TCR down-regulation, point mutated CD3 gamma cDNA was transfected into the CD3 gamma-negative T cell line JGN and CD3 gamma transfectants were analysed. Phosphorylation at S126 but not S123 in the cytoplasmic tail of CD3 gamma was required for PKC-mediated down-regulation of the...... TCR. Furthermore, analysis of a series of CD3 gamma truncation mutants indicated that in addition to S126 phosphorylation a motif C-terminal of S126 was required for TCR down-regulation. Point mutation analyses confirmed this observation and demonstrated that a membrane-proximal di-leucine motif (L131...

  10. Gentamicin binds to the megalin receptor as a competitive inhibitor using the common ligand binding motif of complement type repeats

    DEFF Research Database (Denmark)

    Dagil, Robert; O'Shea, Charlotte; Nykjær, Anders;

    2013-01-01

    Gentamicin is an aminoglycoside widely used in treatments of, in particular, enterococcal, mycobacterial, and severe Gram-negative bacterial infections. Large doses of gentamicin cause nephrotoxicity and ototoxicity, entering the cell via the receptor megalin. Until now, no structural information...

  11. Identification of a novel Stat3 recruitment and activation motif within the granulocyte colony-stimulating factor receptor.

    Science.gov (United States)

    Chakraborty, A; Dyer, K F; Cascio, M; Mietzner, T A; Tweardy, D J

    1999-01-01

    Stat3 is essential for early embryonic development and for myeloid differentiation induced by the cytokines granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6). Two isoforms of Stat3 have been identified, (p92) and beta (p83), which have distinct transcriptional and biological functions. Activation of both Stat3 and Stat3beta requires the distal cytoplasmic domain of the G-CSFR, which contains four Tyr at positions 704, 729, 744, and 764. The studies reported here were undertaken to determine which, if any, of these tyrosine residues participated in Stat3/beta recruitment and activation. We showed that Stat3 and Stat3beta were affinity purified using phosphopeptides containing Y704 and Y744 but not by nonphosphorylated peptide analogues or by phosphopeptides containing Y729 and Y764. Complementary results were obtained in studies examining the ability of these peptides to destabilize and inhibit DNA binding of activated Stat3. Both Y704 and Y744 contributed to optimal activation of Stat3/beta in M1 murine myeloid leukemia cells containing wild-type and Y-to-F mutant G-CSFR constructs. Carboxy-terminal to Y704 at the +3 position is Gln; YXXQ represents a consensus Stat3 recruitment and activation motif. Y744 is followed at the +3 position by Cys (C); YXXC, represents a novel motif implicated in the recruitment and activation of Stat3. Modeling of the SH2 domain of Stat3 based on homologous SH2 domains of known structure revealed polar residues whose side chains contact the +3 position. This substitution may confer specificity for the Y704- and Y744-based ligands by allowing H-bond formation between the binding surface and the Gln or Cys found at the respective +3 position.

  12. Induction of Experimental Arthritis by Borrelial Lipoprotein and CpG Motifs: Are Toll-Like Receptors 2, 4, 9 or CD-14 Involved?

    Energy Technology Data Exchange (ETDEWEB)

    Batsford, S.; Dunn, J.; Mihatsch, M.

    2011-06-01

    Bacterial lipoproteins and CpG-DNA are ligands for Toll-Like-Receptors (TLR) 2 and 9 respectively. Both classes of molecules were reported to induce experimental arthritis in rodents following direct intra-articular injection. Here we studied: (1) whether arthritis induction by Outer surface (Lipo)protein A (OspA) (B.burgdorferi) involved the TLR-2 as well as the TLR-4 or the CD-14 receptors in addition, and (2) re-examined the arthritogenic potential of CpG-DNA motifs in mice. Following intra-articular injection of the test substances [20 {micro}g recombinant, lipidated OspA; 1nM(6 {micro}g) to 10nM(60 {micro}g) synthetic CpG-DNA], inflammation was monitored by {sup 99}Tc scintigraphy (ratio left/right knee joint uptake > 1.1 indicates inflammation) and by histology. Lipoprotein OspA induced severe, acute arthritis in TLR-2{sup +/+} w.t. but not in TLR-2{sup -/-} mice (p<0.01). There were no significant differences in the severity of arthritis induced in TLR-4{sup +/+} w.t. and TLR-4{sup -/-} mutant mice, or between CD14{sup +/+} w.t. and CD14{sup -/-} mice. CpG-DNA (1or 10 nM) did not cause notable inflammation in C57BL/6 mice; {sup 99}Tc ratios were < 1.0 and histology showed only minimal changes. Induction of arthritis by the OspA lipoprotein of B.burgdorferi involves the TLR-2 receptor, no evidence for additional participation of TLR-4 or CD14 receptors was found. Intra-articular injection of CpG-DNA did not produce manifest joint injury in mice, at variance with previous reports.

  13. A Single Amino Acid Mutation (R104P in the E/DRY Motif of GPR40 Impairs Receptor Function.

    Directory of Open Access Journals (Sweden)

    Shimeng Guo

    Full Text Available Type 2 Diabetes Mellitus with insulin resistance, pancreatic β cell dysfunction, and hepatic glucose overproduction is increasing in epidemic proportions worldwide. G protein-coupled receptor 40 (GPR40, a clinically proven anti-diabetic drug target, is mainly expressed in pancreatic β cells and insulin-secreting cell lines. Long chain fatty acids (LCFA increase intracellular calcium concentration and amplify glucose-stimulated insulin secretion by activating GPR40. Here we report that the arginine 104 (R104 is critical for the normal function of GPR40. Mutation of R104 to Proline (R104P results in complete loss of the receptor function. Linoleic acid, ligand of GPR40, could not elicit calcium increase and ERK phosphorylation in cells expressing this mutant receptor. Further study indicated the R104P mutation reduces cell surface localization of GPR40 without affecting the expression of the protein. The small portion of GPR40 R104P mutant that is still located on the membrane has no physiological function, and does not internalize in response to linoleic acid stimulation. These data demonstrate that R104 in GPR40 is critically involved in the normal receptor functions. Interestingly, R104P is a registered single-nucleotide polymorphism of GPR40. The relationship of this GPR40 variant and type 2 diabetes warrants further investigation.

  14. Structural motifs of importance for the constitutive activity of the orphan 7TM receptor EBI2: analysis of receptor activation in the absence of an agonist

    DEFF Research Database (Denmark)

    Benned-Jensen, Tau; Rosenkilde, Mette M

    2008-01-01

    The Epstein-Barr induced receptor 2 (EBI2) is a lymphocyte-expressed orphan seven transmembrane-spanning (7TM) receptor that signals constitutively through Galphai, as shown, for instance by guanosine 5'-O-(3-thio)triphosphate incorporation. Two regions of importance for the constitutive activity...

  15. Structure-Based Analysis of Toxoplasma gondii Profilin: A Parasite-Specific Motif Is Required for Recognition by Toll-Like Receptor 11

    Energy Technology Data Exchange (ETDEWEB)

    K Kucera; A Koblansky; L Saunders; K Frederick; E De La Cruz; S Ghosh; Y Modis

    2011-12-31

    Profilins promote actin polymerization by exchanging ADP for ATP on monomeric actin and delivering ATP-actin to growing filament barbed ends. Apicomplexan protozoa such as Toxoplasma gondii invade host cells using an actin-dependent gliding motility. Toll-like receptor (TLR) 11 generates an innate immune response upon sensing T. gondii profilin (TgPRF). The crystal structure of TgPRF reveals a parasite-specific surface motif consisting of an acidic loop, followed by a long {beta}-hairpin. A series of structure-based profilin mutants show that TLR11 recognition of the acidic loop is responsible for most of the interleukin (IL)-12 secretion response to TgPRF in peritoneal macrophages. Deletion of both the acidic loop and the {beta}-hairpin completely abrogates IL-12 secretion. Insertion of the T. gondii acidic loop and {beta}-hairpin into yeast profilin is sufficient to generate TLR11-dependent signaling. Substitution of the acidic loop in TgPRF with the homologous loop from the apicomplexan parasite Cryptosporidium parvum does not affect TLR11-dependent IL-12 secretion, while substitution with the acidic loop from Plasmodium falciparum results in reduced but significant IL-12 secretion. We conclude that the parasite-specific motif in TgPRF is the key molecular pattern recognized by TLR11. Unlike other profilins, TgPRF slows nucleotide exchange on monomeric rabbit actin and binds rabbit actin weakly. The putative TgPRF actin-binding surface includes the {beta}-hairpin and diverges widely from the actin-binding surfaces of vertebrate profilins.

  16. Secretory TAT-peptide-mediated protein transduction of LIF receptor α-chain distal cytoplasmic motifs into human myeloid HL-60 cells

    Directory of Open Access Journals (Sweden)

    Q. Sun

    2012-10-01

    Full Text Available The distal cytoplasmic motifs of leukemia inhibitory factor receptor α-chain (LIFRα-CT3 can independently induce intracellular myeloid differentiation in acute myeloid leukemia (AML cells by gene transfection; however, there are significant limitations in the potential clinical use of these motifs due to liposome-derived genetic modifications. To produce a potentially therapeutic LIFRα-CT3 with cell-permeable activity, we constructed a eukaryotic expression pcDNA3.0-TAT-CT3-cMyc plasmid with a signal peptide (ss inserted into the N-terminal that codes for an ss-TAT-CT3-cMyc fusion protein. The stable transfection of Chinese hamster ovary (CHO cells via this vector and subsequent selection by Geneticin resulted in cell lines that express and secrete TAT-CT3-cMyc. The spent medium of pcDNA3.0-TAT-CT3-cMyc-transfected CHO cells could be purified using a cMyc-epitope-tag agarose affinity chromatography column and could be detected via SDS-PAGE, with antibodies against cMyc-tag. The direct administration of TAT-CT3-cMyc to HL-60 cell culture media caused the enrichment of CT3-cMyc in the cytoplasm and nucleus within 30 min and led to a significant reduction of viable cells (P < 0.05 8 h after exposure. The advantages of using this mammalian expression system include the ease of generating TAT fusion proteins that are adequately transcripted and the potential for a sustained production of such proteins in vitro for future AML therapy.

  17. Secretory TAT-peptide-mediated protein transduction of LIF receptor α-chain distal cytoplasmic motifs into human myeloid HL-60 cells

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Q. [Department of Hyperbaric Medicine, No. 401 Hospital of PLA, Qingdao (China); Department of Histology and Embryology, Faculty of Basic Medical Sciences, Second Military Medical University, Shanghai (China); Xiong, J. [Department of Histology and Embryology, Faculty of Basic Medical Sciences, Second Military Medical University, Shanghai (China); Lu, J. [Office of Medical Education, Training Department, Second Military Medical University, Shanghai (China); Xu, S. [Department of Histology and Embryology, Faculty of Basic Medical Sciences, Second Military Medical University, Shanghai (China); Li, Y. [State Food and Drug Administration of China,Huangdao Branch, Qingdao (China); Zhong, X.P.; Gao, G.K. [Department of Hyperbaric Medicine, No. 401 Hospital of PLA, Qingdao (China); Liu, H.Q. [2Department of Histology and Embryology, Faculty of Basic Medical Sciences, Second Military Medical University, Shanghai (China)

    2012-06-22

    The distal cytoplasmic motifs of leukemia inhibitory factor receptor α-chain (LIFRα-CT3) can independently induce intracellular myeloid differentiation in acute myeloid leukemia (AML) cells by gene transfection; however, there are significant limitations in the potential clinical use of these motifs due to liposome-derived genetic modifications. To produce a potentially therapeutic LIFRα-CT3 with cell-permeable activity, we constructed a eukaryotic expression pcDNA3.0-TAT-CT3-cMyc plasmid with a signal peptide (ss) inserted into the N-terminal that codes for an ss-TAT-CT3-cMyc fusion protein. The stable transfection of Chinese hamster ovary (CHO) cells via this vector and subsequent selection by Geneticin resulted in cell lines that express and secrete TAT-CT3-cMyc. The spent medium of pcDNA3.0-TAT-CT3-cMyc-transfected CHO cells could be purified using a cMyc-epitope-tag agarose affinity chromatography column and could be detected via SDS-PAGE, with antibodies against cMyc-tag. The direct administration of TAT-CT3-cMyc to HL-60 cell culture media caused the enrichment of CT3-cMyc in the cytoplasm and nucleus within 30 min and led to a significant reduction of viable cells (P < 0.05) 8 h after exposure. The advantages of using this mammalian expression system include the ease of generating TAT fusion proteins that are adequately transcripted and the potential for a sustained production of such proteins in vitro for future AML therapy.

  18. The MHC motif viewer

    DEFF Research Database (Denmark)

    Rapin, Nicolas Philippe Jean-Pierre; Hoof, Ilka; Lund, Ole;

    2010-01-01

    In vertebrates, the onset of cellular immune reactions is controlled by presentation of peptides in complex with major histocompatibility complex (MHC) molecules to T cell receptors. In humans, MHCs are called human leukocyte antigens (HLAs). Different MHC molecules present different subsets of...... peptides, and knowledge of their binding specificities is important for understanding differences in the immune response between individuals. Algorithms predicting which peptides bind a given MHC molecule have recently been developed with high prediction accuracy. The utility of these algorithms is...... binding motif for each MHC molecule is predicted using state-of-the-art, pan-specific peptide-MHC binding-prediction methods, and is visualized as a sequence logo, in a format that allows for a comprehensive interpretation of binding motif anchor positions and amino acid preferences....

  19. Sequence analysis of mouse vomeronasal receptor gene clusters reveals common promoter motifs and a history of recent expansion

    Science.gov (United States)

    Lane, Robert P.; Cutforth, Tyler; Axel, Richard; Hood, Leroy; Trask, Barbara J.

    2002-01-01

    We have analyzed the organization and sequence of 73 V1R genes encoding putative pheromone receptors to identify regulatory features and characterize the evolutionary history of the V1R family. The 73 V1Rs arose from seven ancestral genes around the time of mouse–rat speciation through large local duplications, and this expansion may contribute to speciation events. Orthologous V1R genes appear to have been lost during primate evolution. Exceptional noncoding homology is observed across four V1R subfamilies at one cluster and thus may be important for locus-specific transcriptional regulation. PMID:11752409

  20. C/C-PAA与C/C-FA弯曲性能对比%Comparison of Flexural Properties Between C/C-PAA and C/C-FA

    Institute of Scientific and Technical Information of China (English)

    张万强; 赵英民; 王涛; 詹万初

    2014-01-01

    通过PIP工艺制备了C/C-PAA、C/C-FA复合材料,对PAA、FA裂解碳的XRD、浸渍效果以及C/C-PAA和C/C-FA的弯曲强度进行了分析.结果表明:PAA裂解碳的炭质量、浸渍效果较好,C/C-PAA弯曲强度比C/C-FA弯曲强度高34.9%,弯曲模量对比不明显.

  1. The Necessary Maximality Principle for c.c.c. forcing is equiconsistent with a weakly compact cardinal

    OpenAIRE

    Hamkins, Joel David; Woodin, W. Hugh

    2004-01-01

    The Necessary Maximality Principle for c.c.c. forcing asserts that any statement about a real in a c.c.c. extension that could become true in a further c.c.c. extension and remain true in all subsequent c.c.c. extensions, is already true in the minimal extension containing the real. We show that this principle is equiconsistent with the existence of a weakly compact cardinal.

  2. Sequence analysis, characterization and mRNA distribution of channel catfish (Ictalurus punctatus Rafinesque, 1818) chemokine (C-X-C Motif) receptor 4 (CXCR4) cDNA

    Science.gov (United States)

    Chemokine receptor CXCR4, a member of the G protein-coupled receptor superfamily, binds selectively CXCL12. This protein plays many important roles in immunological as well as pathophysiological functions. In this study, we identified and characterized the channel catfish CXCR4 transcript. The fu...

  3. AptaTRACE Elucidates RNA Sequence-Structure Motifs from Selection Trends in HT-SELEX Experiments.

    Science.gov (United States)

    Dao, Phuong; Hoinka, Jan; Takahashi, Mayumi; Zhou, Jiehua; Ho, Michelle; Wang, Yijie; Costa, Fabrizio; Rossi, John J; Backofen, Rolf; Burnett, John; Przytycka, Teresa M

    2016-07-01

    Aptamers, short RNA or DNA molecules that bind distinct targets with high affinity and specificity, can be identified using high-throughput systematic evolution of ligands by exponential enrichment (HT-SELEX), but scalable analytic tools for understanding sequence-function relationships from diverse HT-SELEX data are not available. Here we present AptaTRACE, a computational approach that leverages the experimental design of the HT-SELEX protocol, RNA secondary structure, and the potential presence of many secondary motifs to identify sequence-structure motifs that show a signature of selection. We apply AptaTRACE to identify nine motifs in C-C chemokine receptor type 7 targeted by aptamers in an in vitro cell-SELEX experiment. We experimentally validate two aptamers whose binding required both sequence and structural features. AptaTRACE can identify low-abundance motifs, and we show through simulations that, because of this, it could lower HT-SELEX cost and time by reducing the number of selection cycles required. PMID:27467247

  4. The arginine of the DRY motif in transmembrane segment III functions as a balancing micro-switch in the activation of the β2-adrenergic receptor

    DEFF Research Database (Denmark)

    Hansen, Louise Valentin; Groenen, Marleen; Nygaard, Rie;

    2012-01-01

    Recent high resolution x-ray structures of the β2-adrenergic receptor confirmed a close salt-bridge interaction between the suspected micro-switch residue ArgIII:26 (Arg3.50) and the neighboring AspIII:25 (Asp3.49). However, neither the expected "ionic lock" interactions between ArgIII:26 and Glu...

  5. The Motif Tracking Algorithm

    CERN Document Server

    Wilson, William; Aickelin, Uwe; 10.1007/s11633.008.0032.0

    2010-01-01

    The search for patterns or motifs in data represents a problem area of key interest to finance and economic researchers. In this paper we introduce the Motif Tracking Algorithm, a novel immune inspired pattern identification tool that is able to identify unknown motifs of a non specified length which repeat within time series data. The power of the algorithm comes from the fact that it uses a small number of parameters with minimal assumptions regarding the data being examined or the underlying motifs. Our interest lies in applying the algorithm to financial time series data to identify unknown patterns that exist. The algorithm is tested using three separate data sets. Particular suitability to financial data is shown by applying it to oil price data. In all cases the algorithm identifies the presence of a motif population in a fast and efficient manner due to the utilisation of an intuitive symbolic representation. The resulting population of motifs is shown to have considerable potential value for other ap...

  6. The Motif Tracking Algorithm

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The search for patterns or motifs in data represents a problem area of key interest to finance and economic researchers. In this paper, we introduce the motif tracking algorithm (MTA), a novel immune inspired (IS) pattern identification tool that is able to identify unknown motifs of a non specified length which repeat within time series data. The power of the algorithm comes from the fact that it uses a small number of parameters with minimal assumptions regarding the data being examined or the underlying motifs. Our interest lies in applying the algorithm to financial time series data to identify unknown patterns that exist. The algorithm is tested using three separate data sets. Particular suitability to financial data is shown by applying it to oil price data. In all cases, the algorithm identifies the presence of a motif population in a fast and efficient manner due to the utilization of an intuitive symbolic representation.The resulting population of motifs is shown to have considerable potential value for other applications such as forecasting and algorithm seeding.

  7. Sequence similarity between the erythrocyte binding domain of the Plasmodium vivax Duffy binding protein and the V3 loop of HIV-1 strain MN reveals a functional heparin binding motif involved in binding to the Duffy antigen receptor for chemokines

    Directory of Open Access Journals (Sweden)

    Bolton Michael J

    2011-11-01

    Full Text Available Abstract Background The HIV surface glycoprotein gp120 (SU, gp120 and the Plasmodium vivax Duffy binding protein (PvDBP bind to chemokine receptors during infection and have a site of amino acid sequence similarity in their binding domains that often includes a heparin binding motif (HBM. Infection by either pathogen has been found to be inhibited by polyanions. Results Specific polyanions that inhibit HIV infection and bind to the V3 loop of X4 strains also inhibited DBP-mediated infection of erythrocytes and DBP binding to the Duffy Antigen Receptor for Chemokines (DARC. A peptide including the HBM of PvDBP had similar affinity for heparin as RANTES and V3 loop peptides, and could be specifically inhibited from heparin binding by the same polyanions that inhibit DBP binding to DARC. However, some V3 peptides can competitively inhibit RANTES binding to heparin, but not the PvDBP HBM peptide. Three other members of the DBP family have an HBM sequence that is necessary for erythrocyte binding, however only the protein which binds to DARC, the P. knowlesi alpha protein, is inhibited by heparin from binding to erythrocytes. Heparitinase digestion does not affect the binding of DBP to erythrocytes. Conclusion The HBMs of DBPs that bind to DARC have similar heparin binding affinities as some V3 loop peptides and chemokines, are responsible for specific sulfated polysaccharide inhibition of parasite binding and invasion of red blood cells, and are more likely to bind to negative charges on the receptor than cell surface glycosaminoglycans.

  8. Identification of a novel protein-protein interaction motif mediating interaction of GPCR-associated sorting proteins with G protein-coupled receptors

    DEFF Research Database (Denmark)

    Bornert, Olivier; Møller, Thor Christian; Boeuf, Julien;

    2013-01-01

    GPCR desensitization and down-regulation are considered key molecular events underlying the development of tolerance in vivo. Among the many regulatory proteins that are involved in these complex processes, GASP-1 have been shown to participate to the sorting of several receptors toward the degra......GPCR desensitization and down-regulation are considered key molecular events underlying the development of tolerance in vivo. Among the many regulatory proteins that are involved in these complex processes, GASP-1 have been shown to participate to the sorting of several receptors toward...... the degradation pathway. This protein belongs to the recently identified GPCR-associated sorting proteins (GASPs) family that comprises ten members for which structural and functional details are poorly documented. We present here a detailed structure-function relationship analysis of the molecular interaction...... between GASPs and a panel of GPCRs. In a first step, GST-pull down experiments revealed that all the tested GASPs display significant interactions with a wide range of GPCRs. Importantly, the different GASP members exhibiting the strongest interaction properties were also characterized by the presence...

  9. Automatic Network Fingerprinting through Single-Node Motifs

    CERN Document Server

    Echtermeyer, Christoph; Rodrigues, Francisco A; Kaiser, Marcus; 10.1371/journal.pone.0015765

    2011-01-01

    Complex networks have been characterised by their specific connectivity patterns (network motifs), but their building blocks can also be identified and described by node-motifs---a combination of local network features. One technique to identify single node-motifs has been presented by Costa et al. (L. D. F. Costa, F. A. Rodrigues, C. C. Hilgetag, and M. Kaiser, Europhys. Lett., 87, 1, 2009). Here, we first suggest improvements to the method including how its parameters can be determined automatically. Such automatic routines make high-throughput studies of many networks feasible. Second, the new routines are validated in different network-series. Third, we provide an example of how the method can be used to analyse network time-series. In conclusion, we provide a robust method for systematically discovering and classifying characteristic nodes of a network. In contrast to classical motif analysis, our approach can identify individual components (here: nodes) that are specific to a network. Such special nodes...

  10. Visibility graph motifs

    CERN Document Server

    Iacovacci, Jacopo

    2015-01-01

    Visibility algorithms transform time series into graphs and encode dynamical information in their topology, paving the way for graph-theoretical time series analysis as well as building a bridge between nonlinear dynamics and network science. In this work we introduce and study the concept of visibility graph motifs, smaller substructures that appear with characteristic frequencies. We develop a theory to compute in an exact way the motif profiles associated to general classes of deterministic and stochastic dynamics. We find that this simple property is indeed a highly informative and computationally efficient feature capable to distinguish among different dynamics and robust against noise contamination. We finally confirm that it can be used in practice to perform unsupervised learning, by extracting motif profiles from experimental heart-rate series and being able, accordingly, to disentangle meditative from other relaxation states. Applications of this general theory include the automatic classification a...

  11. TNFα modulates Fibroblast Growth Factor Receptor 2 gene expression through the pRB/E2F1 pathway: identification of a non-canonical E2F binding motif.

    Directory of Open Access Journals (Sweden)

    Sirio D'Amici

    Full Text Available Interactions between epithelium and mesenchyme during wound healing are not fully understood, but Fibroblast Growth Factors (FGFs and their receptors FGFRs are recognized as key elements. FGFR2 gene encodes for two splicing transcript variants, FGFR2-IIIb or Keratinocyte Growth Factor Receptor (KGFR and FGFR2-IIIc, which differ for tissue localization and ligand specificity. Proinflammatory cytokines play an essential role in the regulation of epithelial-mesenchymal interactions, and have been indicated to stimulate FGFs production. Here we demonstrated that upregulation of FGFR2 mRNA and protein expression is induced by the proinflammatory cytokines Tumor Necrosis Factor-α, Interleukin-1β and Interleukin 2. Furthermore, we found that TNFα determines FGFR2 transcriptional induction through activation of pRb, mediated by Raf and/or p38 pathways, and subsequent release of the transcription factor E2F1. Experiments based on FGFR2 promoter serial deletions and site-directed mutagenesis allowed us to identify a minimal responsive element that retains the capacity to be activated by E2F1. Computational analysis indicated that this element is a non-canonical E2F responsive motif. Thus far, the molecular mechanisms of FGFR2 upregulation during wound healing or in pathological events are not known. Our data suggest that FGFR2 expression can be modulated by local recruitment of inflammatory cytokines. Furthermore, since alterations in FGFR2 expression have been linked to the pathogenesis of certain human cancers, these findings could also provide elements for diagnosis and potential targets for novel therapeutic approaches.

  12. Thermoelectric properties of porous SiC/C composites

    NARCIS (Netherlands)

    Fujisawa, Masashi; Hata, Toshimitsu; Kitagawa, Hiroyuki; Bronsveld, Paul; Suzuki, Youki; Hasezaki, Kazuhiro; Noda, Yasutoshi; Imamura, Yuji

    2008-01-01

    We developed a porous SiC/C composite by oxidizing a SiC/C composite made from a mixed powder of wood charcoal and SiO2 (32-45 mu m) by pulse current sintering at 1600 and 1800 degrees C under a N-2 atmosphere. The microstructures of the porous SiC/C composites with oxidation and the SiC/C composite

  13. A single lysine of the two-lysine recognition motif of the D3 domain of receptor-associated protein is sufficient to mediate endocytosis by low-density lipoprotein receptor-related protein.

    Science.gov (United States)

    van den Biggelaar, Maartje; Sellink, Erica; Klein Gebbinck, Jacqueline W T M; Mertens, Koen; Meijer, Alexander B

    2011-03-01

    Ligand binding of the low-density lipoprotein (LDL) receptor family is mediated by complement-type repeats (CR) each comprising a binding pocket for a single basic amino acid residue. It has been proposed that at least two CRs are required for high-affinity interaction by utilising two spatially distinct lysine residues on the ligand surface. LDL receptor-related protein (LRP) mediates the cellular uptake of a multitude of ligands, some of which bind LRP with a relatively low affinity suggesting a suboptimal positioning of the two critical lysines. We now addressed the role of the two critical lysines not only in LRP binding but also in LRP-dependent endocytosis. Variants of the third domain (D3) of receptor-associated protein (RAP) were created carrying lysine to alanine or arginine replacements at the putative contact residues K253, K256 and K270. Surface plasmon resonance revealed that replacement of K253 did not affect high-affinity LRP binding at all, whereas replacement of either K256 or K270 markedly reduced the affinity by approximately 10-fold. Binding was abolished when both lysines were replaced. Substitution by either alanine or arginine exerted an almost identical effect on LRP binding. This suggests that despite their positive charge, arginine residues do not support receptor binding at all. Confocal microscopy and flow cytometry studies surprisingly revealed that the single mutants were still taken up and still competed for the uptake of full length RAP despite their receptor binding defect. We therefore propose that the presence of only one of the two critical lysines is sufficient to drive endocytosis. PMID:21144910

  14. Silencing of reversion-inducing cysteine-rich protein with Kazal motifs stimulates hyperplastic phenotypes through activation of epidermal growth factor receptor and hypoxia-inducible factor-2α.

    Directory of Open Access Journals (Sweden)

    You Mie Lee

    Full Text Available Reversion-inducing cysteine-rich protein with Kazal motifs (RECK, a tumor suppressor is down-regulated by the oncogenic signals and hypoxia, but the biological function of RECK in early tumorigenic hyperplastic phenotypes is largely unknown. Knockdown of RECK by small interfering RNA (siRECK or hypoxia significantly promoted cell proliferation in various normal epithelial cells. Hypoxia as well as knockdown of RECK by siRNA increased the cell cycle progression, the levels of cyclin D1 and c-Myc, and the phosphorylation of Rb protein (p-pRb, but decreased the expression of p21(cip1, p27(kip1, and p16(ink4A. HIF-2α was upregulated by knockdown of RECK, indicating HIF-2α is a downstream target of RECK. As knockdown of RECK induced the activation of epidermal growth factor receptor (EGFR and treatment of an EGFR kinase inhibitor, gefitinib, suppressed HIF-2α expression induced by the silencing of RECK, we can suggest that the RECK silenicng-EGFR-HIF-2α axis might be a key molecular mechanism to induce hyperplastic phenotype of epithelial cells. It was also found that shRNA of RECK induced larger and more numerous colonies than control cells in an anchorage-independent colony formation assay. Using a xenograft assay, epithelial cells with stably transfected with shRNA of RECK formed a solid mass earlier and larger than those with control cells in nude mice. In conclusion, the suppression of RECK may promote the development of early tumorigenic hyperplastic characteristics in hypoxic stress.

  15. Mining protein sequences for motifs.

    Science.gov (United States)

    Narasimhan, Giri; Bu, Changsong; Gao, Yuan; Wang, Xuning; Xu, Ning; Mathee, Kalai

    2002-01-01

    We use methods from Data Mining and Knowledge Discovery to design an algorithm for detecting motifs in protein sequences. The algorithm assumes that a motif is constituted by the presence of a "good" combination of residues in appropriate locations of the motif. The algorithm attempts to compile such good combinations into a "pattern dictionary" by processing an aligned training set of protein sequences. The dictionary is subsequently used to detect motifs in new protein sequences. Statistical significance of the detection results are ensured by statistically determining the various parameters of the algorithm. Based on this approach, we have implemented a program called GYM. The Helix-Turn-Helix motif was used as a model system on which to test our program. The program was also extended to detect Homeodomain motifs. The detection results for the two motifs compare favorably with existing programs. In addition, the GYM program provides a lot of useful information about a given protein sequence. PMID:12487759

  16. MHC motif viewer

    DEFF Research Database (Denmark)

    Rapin, Nicolas Philippe Jean-Pierre; Hoof, Ilka; Lund, Ole;

    2008-01-01

    In vertebrates, the major histocompatibility complex (MHC) presents peptides to the immune system. In humans, MHCs are called human leukocyte antigens (HLAs), and some of the loci encoding them are the most polymorphic in the human genome. Different MHC molecules present different subsets of....... Algorithms that predict which peptides MHC molecules bind have recently been developed and cover many different alleles, but the utility of these algorithms is hampered by the lack of tools for browsing and comparing the specificity of these molecules. We have, therefore, developed a web server, MHC motif...

  17. High Affinity Heme Binding to a Heme Regulatory Motif on the Nuclear Receptor Rev-erbβ Leads to Its Degradation and Indirectly Regulates Its Interaction with Nuclear Receptor Corepressor.

    Science.gov (United States)

    Carter, Eric L; Gupta, Nirupama; Ragsdale, Stephen W

    2016-01-29

    Rev-erbα and Rev-erbβ are heme-binding nuclear receptors (NR) that repress the transcription of genes involved in regulating metabolism, inflammation, and the circadian clock. Previous gene expression and co-immunoprecipitation studies led to a model in which heme binding to Rev-erbα recruits nuclear receptor corepressor 1 (NCoR1) into an active repressor complex. However, in contradiction, biochemical and crystallographic studies have shown that heme decreases the affinity of the ligand-binding domain of Rev-erb NRs for NCoR1 peptides. One explanation for this discrepancy is that the ligand-binding domain and NCoR1 peptides used for in vitro studies cannot replicate the key features of the full-length proteins used in cellular studies. However, the combined in vitro and cellular results described here demonstrate that heme does not directly promote interactions between full-length Rev-erbβ (FLRev-erbβ) and an NCoR1 construct encompassing all three NR interaction domains. NCoR1 tightly binds both apo- and heme-replete FLRev-erbβ·DNA complexes; furthermore, heme, at high concentrations, destabilizes the FLRev-erbβ·NCoR1 complex. The interaction between FLRev-erbβ and NCoR1 as well as Rev-erbβ repression at the Bmal1 promoter appear to be modulated by another cellular factor(s), at least one of which is related to the ubiquitin-proteasome pathway. Our studies suggest that heme is involved in regulating the degradation of Rev-erbβ in a manner consistent with its role in circadian rhythm maintenance. Finally, the very slow rate constant (10(-6) s(-1)) of heme dissociation from Rev-erbβ rules out a prior proposal that Rev-erbβ acts as an intracellular heme sensor.

  18. Downregulation of 5-HT7 Serotonin Receptors by the Atypical Antipsychotics Clozapine and Olanzapine. Role of Motifs in the C-Terminal Domain and Interaction with GASP-1

    DEFF Research Database (Denmark)

    Manfra, Ornella; Van Craenenbroeck, Kathleen; Skieterska, Kamila;

    2015-01-01

    The human 5-HT7 serotonin receptor, a G-protein-coupled receptor (GPCR), activates adenylyl cyclase constitutively and upon agonist activation. Biased ligands differentially activate 5-HT7 serotonin receptor desensitization, internalization and degradation in addition to G protein activation. We......-mediated degradation of 5-HT7 receptors and also interfered with G protein activation. In addition, we tested whether receptor degradation was mediated by the GPCR-associated sorting protein-1 (GASP-1). We show that GASP-1 binds the 5-HT7 receptor and regulates the clozapine-mediated degradation. Mutations...

  19. The MHC motif viewer: a visualization tool for MHC binding motifs

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Hoof, Ilka; Lund, Ole;

    2010-01-01

    In vertebrates, the onset of cellular immune reactions is controlled by presentation of peptides in complex with major histocompatibility complex (MHC) molecules to T cell receptors. In humans, MHCs are called human leukocyte antigens (HLAs). Different MHC molecules present different subsets of...... peptides, and knowledge of their binding specificities is important for understanding differences in the immune response between individuals. Algorithms predicting which peptides bind a given MHC molecule have recently been developed with high prediction accuracy. The utility of these algorithms is...... binding motif for each MHC molecule is predicted using state-of-the-art, pan-specific peptide-MHC binding-prediction methods, and is visualized as a sequence logo, in a format that allows for a comprehensive interpretation of binding motif anchor positions and amino acid preferences....

  20. Testing of DLR C/C-SiC and C/C for HIFiRE 8 Scramjet Combustor

    Science.gov (United States)

    Glass, David E.; Capriotti, Diego P.; Reimer, Thomas; Kutemeyer, Marius; Smart, Michael K.

    2014-01-01

    Ceramic Matrix Composites (CMCs) have been proposed for use as lightweight hot structures in scramjet combustors. Previous studies have calculated significant weight savings by utilizing CMCs (active and passive) versus actively cooled metallic scramjet structures. Both a carbon/carbon (C/C) and a carbon/carbon-silicon carbide (C/C-SiC) material fabricated by DLR (Stuttgart, Germany) are being considered for use in a passively cooled combustor design for Hypersonic International Flight Research Experimentation (HIFiRE) 8, a joint Australia / Air Force Research Laboratory hypersonic flight program, expected to fly at Mach 7 for approximately 30 sec, at a dynamic pressure of 55 kilopascals. Flat panels of the DLR C/C and C/C-SiC materials were installed downstream of a hydrogen-fueled, dual-mode scramjet combustor and tested for several minutes at conditions simulating flight at Mach 5 and Mach 6. Gaseous hydrogen fuel was used to fuel the scramjet combustor. The test panels were instrumented with embedded Type K and Type S thermocouples. Zirconia felt insulation was used during some of the tests to reduce heat loss from the back surface and thus increase the heated surface temperature of the C/C-SiC panel approximately 177 C (350 F). The final C/C-SiC panel was tested for three cycles totaling over 135 sec at Mach 6 enthalpy. Slightly more erosion was observed on the C/C panel than the C/C-SiC panels, but both material systems demonstrated acceptable recession performance for the HIFiRE 8 flight.

  1. Internal friction and gas desorption of {C}/{C} composites

    Science.gov (United States)

    Serizawa, H.; Sato, S.; Kohyama, A.

    1994-09-01

    {C}/{C} composites are the most promising candidates as high heat flux component materials, where temperature dependence of mechanical properties and gas desorption behavior at elevated temperature are important properties. At the beginning, the newly developed internal friction measurement apparatus, which enables the accurate measurement of dynamic elastic properties up to 1373 K along with the measurement of gas desorption behavior, was used. The materials studied were unidirectional (UD) {C}/{C} composites reinforced with mesophase pitch-based carbon fibers, which were heat treated at temperatures ranging from 1473 to 2773 K which produced a variety of graphitized microstructures. Two-dimensional (2D) {C}/{C} composites reinfored with flat woven fabrics of PAN type carbon fibers were also studied. These materials were heat treated at 1873 K. From the temperature spectrum of internal friction of 2D {C}/{C} composites, these internal friction peaks were detected and were related to gas desorption. Also the temperature dependence of Young's modulus of UD {C}/{C} composites, negative and positive dependence of Young's modulus were observed reflecting microstructure changes resulting from the heat treatments.

  2. Efficient C/C++ programming smaller, faster, better

    CERN Document Server

    Heller, Steve

    1994-01-01

    Efficient C/C++ Programming describes a practical, real-world approach to efficient C/C++ programming. Topics covered range from how to save storage using a restricted character set and how to speed up access to records by employing hash coding and caching. A selective mailing list system is used to illustrate rapid access to and rearrangement of information selected by criteria specified at runtime.Comprised of eight chapters, this book begins by discussing factors to consider when deciding whether a program needs optimization. In the next chapter, a supermarket price lookup system is used to

  3. One motif to bind them: A small-XXX-small motif affects transmembrane domain 1 oligomerization, function, localization, and cross-talk between two yeast GPCRs.

    Science.gov (United States)

    Lock, Antonia; Forfar, Rachel; Weston, Cathryn; Bowsher, Leo; Upton, Graham J G; Reynolds, Christopher A; Ladds, Graham; Dixon, Ann M

    2014-12-01

    G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors in mammals and facilitate a range of physiological responses triggered by a variety of ligands. GPCRs were thought to function as monomers, however it is now accepted that GPCR homo- and hetero-oligomers also exist and influence receptor properties. The Schizosaccharomyces pombe GPCR Mam2 is a pheromone-sensing receptor involved in mating and has previously been shown to form oligomers in vivo. The first transmembrane domain (TMD) of Mam2 contains a small-XXX-small motif, overrepresented in membrane proteins and well-known for promoting helix-helix interactions. An ortholog of Mam2 in Saccharomyces cerevisiae, Ste2, contains an analogous small-XXX-small motif which has been shown to contribute to receptor homo-oligomerization, localization and function. Here we have used experimental and computational techniques to characterize the role of the small-XXX-small motif in function and assembly of Mam2 for the first time. We find that disruption of the motif via mutagenesis leads to reduction of Mam2 TMD1 homo-oligomerization and pheromone-responsive cellular signaling of the full-length protein. It also impairs correct targeting to the plasma membrane. Mutation of the analogous motif in Ste2 yielded similar results, suggesting a conserved mechanism for assembly. Using co-expression of the two fungal receptors in conjunction with computational models, we demonstrate a functional change in G protein specificity and propose that this is brought about through hetero-dimeric interactions of Mam2 with Ste2 via the complementary small-XXX-small motifs. This highlights the potential of these motifs to affect a range of properties that can be investigated in other GPCRs.

  4. Get more control over your C/C++ service

    CERN Document Server

    CERN. Geneva

    2015-01-01

    Are you looking for a way to better diagnose or monitor your C/C++ programs? Find out more about CMX - a neat, lightweight library (<32Kb) which targets this need. It allows to expose information from inside a process through a simple API, enabling pre-failure detection in combination with your favourite monitoring system.

  5. Oxidative electrochemical aryl C-C coupling of spiropyrans

    NARCIS (Netherlands)

    Ivashenko, Oleksii; van Herpt, Jochem T.; Rudolf, Petra; Feringa, Ben L.; Browne, Wesley R.

    2013-01-01

    The isolation and definitive assignment of the species formed upon electrochemical oxidation of nitro-spiropyran (SP) is reported. The oxidative aryl C-C coupling at the indoline moiety of the SP radical cation to form covalent dimers of the ring-closed SP form is demonstrated. The coupling is block

  6. Deformation microstructure and orientation of F.C.C. crystals

    DEFF Research Database (Denmark)

    Liu, Q.; Hansen, N.

    1995-01-01

    The effect of crystallographic orientation on the microstructural evolution in f.c.c. metals with medium to high stacking fault energy is analyzed. This analysis is based on a literature review of the behaviour of single crystals and polycrystals supplemented with an experimental study of cold...

  7. Interstellar detection of c-C3D2

    CERN Document Server

    Spezzano, S; Schilke, P; Caselli, P; Menten, K M; McCarthy, M C; Bizzocchi, L; Trevino-Morales, S P; Aikawa, Y; Schlemmer, S

    2013-01-01

    We report the first interstellar detection of c-C3D2. The doubly deuterated cyclopropenylidene, a carbene, has been detected toward the starless cores TMC- 1C and L1544 using the IRAM 30m telescope. The J(Ka,Kc) = 3(0,3)-2(1,2), 3(1,3)-2(0,2), and 2(2,1)-1(1,0) transitions of this species have been observed at 3 mm in both sources. The expected 1:2 intensity ratio has been found in the 3(0,3)-2(1,2) and 3(1,3)-2(0,2) lines, belonging to the para and ortho species respectively. We also observed lines of the main species, c-C3H2, the singly deuterated c-C3HD, and the species with one 13C off of the principal axis of the molecule, c-H13CC2H. The lines of c-C3D2 have been observed with high signal to noise ratio, better than 7.5 sigma in TMC-1C and 9 sigma in L1544. The abundance of doubly deuterated cyclopropenylidene with respect to the normal species is found to be (0.4 - 0.8)% in TMC-1C and (1.2 - 2.1)% in L1544. The deuteration of this small hydrocarbon ring is analysed with a comprehensive gas-grain model, ...

  8. Sequential visibility-graph motifs

    Science.gov (United States)

    Iacovacci, Jacopo; Lacasa, Lucas

    2016-04-01

    Visibility algorithms transform time series into graphs and encode dynamical information in their topology, paving the way for graph-theoretical time series analysis as well as building a bridge between nonlinear dynamics and network science. In this work we introduce and study the concept of sequential visibility-graph motifs, smaller substructures of n consecutive nodes that appear with characteristic frequencies. We develop a theory to compute in an exact way the motif profiles associated with general classes of deterministic and stochastic dynamics. We find that this simple property is indeed a highly informative and computationally efficient feature capable of distinguishing among different dynamics and robust against noise contamination. We finally confirm that it can be used in practice to perform unsupervised learning, by extracting motif profiles from experimental heart-rate series and being able, accordingly, to disentangle meditative from other relaxation states. Applications of this general theory include the automatic classification and description of physical, biological, and financial time series.

  9. Main: SEF1MOTIF [PLACE

    Lifescience Database Archive (English)

    Full Text Available inding motif; sequence found in 5'-upstream region (-640; -765) of soybean beta-conglicinin (7S globulin) ge...ne; W=A/T; SOYBEAN; STORAGE PROTEIN; 7S; GLOBULIN; BETA-CONGLICININ; seed; soybean (Glycine max) ATATTTAWW ...

  10. Reference: TCA1MOTIF [PLACE

    Lifescience Database Archive (English)

    Full Text Available TCA1MOTIF Goldsbrough AP, Albrecht H, Stratford R Salicylic acid-inducible binding ...of a tobacco nuclear protein to a 10 bp sequence which is highly conserved amongst stress-inducible genes. Plant J 3:563-571 (1993) PubMed: 8220463; ...

  11. Direct, Sequential, and Stereoselective Alkynylation of C,C-Dibromophosphaalkenes.

    Science.gov (United States)

    Shameem, Muhammad A; Esfandiarfard, Keyhan; Öberg, Elisabet; Ott, Sascha; Orthaber, Andreas

    2016-07-18

    The first direct alkynylation of C,C-dibromophosphaalkenes by a reaction with sulfonylacetylenes is reported. Alkynylation proceeds selectively in the trans position relative to the P substituent to afford bromoethynylphosphaalkenes. Owing to the absence of transition metals in the procedure, the previously observed conversion of dibromophosphaalkenes into phosphaalkynes through the phosphorus analog of the Fritsch-Buttenberg-Wiechell rearrangement is thus suppressed. The bromoethynylphosphaalkenes can subsequently be converted to C,C-diacetylenic, cross-conjugated phosphaalkenes by following a Sonogashira coupling protocol in good overall yields. By using the newly described method, full control over the stereochemistry at the P=C double bond is achieved. The substrate scope of this reaction is demonstrated for different dibromophosphaalkenes as well as different sulfonylacetylenes. PMID:27310813

  12. [Study on spectral emissivity of C/C composites].

    Science.gov (United States)

    Zhu, Bo; Cao, Wei-Wei; Jing, Min; Dong, Xing-Guang; Wang, Cheng-Guo

    2009-11-01

    Different types of C/C composites were prepared by conventional molding, and the changes in normal spectral emissivity of samples were tested. The testing results show that spectral emissivity of C/C composite reinforced by short cut carbon fibers is generally higher than the sample reinforced by carbon cloth in the entire 2500-13000nm wavelength region. The structure of short cut carbon fibers is relatively loose and the number of material particles is less than other samples in unit volume, which increases the penetration depth of electromagnetic waves. This is the reason for higher normal spectral emissivity and better heat radiation property. Meanwhile, the test results of normal spectral emissivity for fiber perform and C/C composite samples show that the spectral emissivity of resin carbon is better than fiber carbon because of the difference in microstructure for the two kinds of carbon materials. Laser Raman spectroscopy was employed to analyze the microstructures of different carbon materials, and the results show that because sp3 and sp2 hybrid states of carbon atoms in resin carbon produced more vibration modes, the resin carbon also has higher normal spectral emissivity and better characteristics of heat radiation.

  13. Dynamic analysis of C/C composite finger seal

    Institute of Scientific and Technical Information of China (English)

    Chen Guoding; Wang Li’na; Yu Qiangpeng; Su Hua

    2014-01-01

    A seal device as an important component of aeroengines has decisive influence on per-formance, reliability, and working life of aeroengines. With the development of aeroengines, demands on the performance characteristics of seal devices are made strictly. Finger seal as a novel kind of sealing device, recently attracts more and more attentions in academic circles and engineer-ing fields at home and abroad. Research on finger seals has been extensively developed, especially on leakage and wear performances under dynamic conditions. However, it is a pity that the work on finger seals has been limited with a single approach that is improving the performance by structural optimization;in addition, the technology of dynamic analysis on finger seals is weak. Aiming at the problems mentioned above, a distributed mass equivalent dynamic model of finger seals considering the coupling effect of overlaid laminates is established in the present paper, the dynamic perfor-mance of 2.5 dimension C/C composite finger seal is analyzed with the model, and then the effects of fiber bundle density and fiber bundle preparation direction on finger seal’s dynamic performance are discussed, as well as compared with those of Co-based alloy finger seal. The current work is about dynamic analysis of finger seals and application of C/C composite in this paper may have much academic significance and many engineering values for improving research level of finger seal dynamics and exploring feasibility of C/C composite being used for finger seals.

  14. [Study on spectral emissivity of C/C composites].

    Science.gov (United States)

    Zhu, Bo; Cao, Wei-Wei; Jing, Min; Dong, Xing-Guang; Wang, Cheng-Guo

    2009-11-01

    Different types of C/C composites were prepared by conventional molding, and the changes in normal spectral emissivity of samples were tested. The testing results show that spectral emissivity of C/C composite reinforced by short cut carbon fibers is generally higher than the sample reinforced by carbon cloth in the entire 2500-13000nm wavelength region. The structure of short cut carbon fibers is relatively loose and the number of material particles is less than other samples in unit volume, which increases the penetration depth of electromagnetic waves. This is the reason for higher normal spectral emissivity and better heat radiation property. Meanwhile, the test results of normal spectral emissivity for fiber perform and C/C composite samples show that the spectral emissivity of resin carbon is better than fiber carbon because of the difference in microstructure for the two kinds of carbon materials. Laser Raman spectroscopy was employed to analyze the microstructures of different carbon materials, and the results show that because sp3 and sp2 hybrid states of carbon atoms in resin carbon produced more vibration modes, the resin carbon also has higher normal spectral emissivity and better characteristics of heat radiation. PMID:20101951

  15. Dynamic analysis of C/C composite finger seal

    Directory of Open Access Journals (Sweden)

    Chen Guoding

    2014-06-01

    Full Text Available A seal device as an important component of aeroengines has decisive influence on performance, reliability, and working life of aeroengines. With the development of aeroengines, demands on the performance characteristics of seal devices are made strictly. Finger seal as a novel kind of sealing device, recently attracts more and more attentions in academic circles and engineering fields at home and abroad. Research on finger seals has been extensively developed, especially on leakage and wear performances under dynamic conditions. However, it is a pity that the work on finger seals has been limited with a single approach that is improving the performance by structural optimization; in addition, the technology of dynamic analysis on finger seals is weak. Aiming at the problems mentioned above, a distributed mass equivalent dynamic model of finger seals considering the coupling effect of overlaid laminates is established in the present paper, the dynamic performance of 2.5 dimension C/C composite finger seal is analyzed with the model, and then the effects of fiber bundle density and fiber bundle preparation direction on finger seal’s dynamic performance are discussed, as well as compared with those of Co-based alloy finger seal. The current work is about dynamic analysis of finger seals and application of C/C composite in this paper may have much academic significance and many engineering values for improving research level of finger seal dynamics and exploring feasibility of C/C composite being used for finger seals.

  16. Borane-catalyzed cracking of C-C bonds in coal; Boran-katalysierte C-C-Bindungungsspaltung in Steinkohle

    Energy Technology Data Exchange (ETDEWEB)

    Narangerel, J.; Haenel, M.W. [Max-Planck-Institut fuer Kohlenforschung, Muelheim an der Ruhr (Germany)

    1998-09-01

    Coal, especially coking coal, was reacted with hydrogen at comparatively mild reaction conditions (150-280 degrees centigrade, 20 MPa hydrogen pressure) in the presence of catalysts consisting of borange reagents and certain transition metal halides to obtaine more than 80 percent of pyridine-soluble products. The influence of the degree of coalification, catalyst and temperature on the borane-catalyzed hydrogenolysis of C-C bonds in coal was investigated. (orig.) [Deutsch] Steinkohlen, insbesondere im Inkohlungsbereich der Fettkohlen (Kokskohlen), werden in Gegenwart von Katalysatoren aus Boran-Reagentien und bestimmten Uebergangsmetallhalogeniden mit Wasserstoff bei vergleichsweise milden Reaktionsbedingungen (250-280 C, 20 MPa Wasserstoffdruck) in zu ueber 80% pyridinloesliche Produkte umgewandelt. Der Einfluss von Inkohlungsgrad, Katalysator und Temperatur auf die Boran-katalysierte C-C-Bindungshydrogenolyse in Kohle wurde untersucht. (orig.)

  17. Interleukin-24 inhibits tumor cell metastasis through (C-X-C motif) ligand 12/(C-X-C motif) receptor 4 signal axis%白细胞介素-24通过CXC趋化因子配体12/CXC趋化因子受体4信号轴抑制肿瘤细胞转移

    Institute of Scientific and Technical Information of China (English)

    杨俊波; 黄晓洁

    2015-01-01

    目的 探讨白细胞介素(IL)-24在体外实验中通过抑制CXC趋化因子配体12/CXC趋化因子受体4 (CXCL12/CXCR4)信号轴而抑制肺癌细胞迁移和侵袭.方法 以慢病毒介导IL-24基因转染H1299细胞为研究对象,研究IL-24对CXCL12/CXCR4信号轴的抑制作用.采用Western blot和Transwell细胞迁移及细胞侵袭实验评价其生物学效应.结果 IL-24在H1299-IL24细胞中的表达明显抑制了CXCR4 mRNA及蛋白的表达(P<0.05).IL-24通过下调CXCR4的表达明显抑制了肿瘤细胞的迁移和侵袭,H1299-IL24细胞的迁移数量较对照细胞下降了约30%,侵袭能力比较对照组下降30% ~40%,此外IL-24联合CXCR4抑制剂AMD3100使用时,表现出对肿瘤细胞迁移能力更强的抑制能力(P<0.05).结论 IL-24通过抑制CXCL12/CXCR4信号通路,从而抑制肿瘤细胞的迁移和侵袭.此外,当IL-24联合CXCR4抑制剂使用时,表现出更强的对抗肿瘤转移的能力.%Objective To investigate whetheinterleukin-24 (IL-24) could inhibithe chemokine (C-X-motif) ligand (CXCL)-12/chemokine (C-X-motif) recepto(CXCR)-4 signaling pathway and suppreslung cancecell migration and invasion in vitro.MethodThe lung cancecell line H1299 wastably transfected with recombinanlentiviral vectorharboring open reading frame (ORF) of IL-24 and used in the presenstudy to determine the inhibitory effectof IL-24 on CXCL12/CXCR4 axis.The inhibitory effectof IL-24 on CXCL12/CXCR4 were assessed by Western blotting.Biological function wastudied using cell migration and invasion assays.ResultIL-24 expression in the H1299-IL24 cell line resulted in reduced CXCR4 expression on both mRNand protein level(P < 0.05).Functional studieshowed thaIL-24 inhibited tumocell migration (30% decrease) and invasion (30%-40% decrease, P <0.05).Finally, IL-24, when combined with CXCR4 inhibito(AMD3100), demonstrated enhanced inhibitory activity on tumocell migration (P < 0.05).Conclusion IL-24 interferewith the CXCL12

  18. Effect of HfC on the ablative and mechanical properties of C/C composites

    International Nuclear Information System (INIS)

    The ablation and mechanical behavior of the carbon/carbon (C/C) and hafnium carbide (HfC) modified C/C (HfC-C/C) composites were evaluated by oxyacetylene flame and the three-point bending tests. The effect of impact damage on their mechanical behavior was also investigated. To produce the HfC-C/C composites, the refractory carbide precursor was introduced to the preforms by impregnating with HfOCl2.8H2O solution. Both the C/C and the HfC-C/C preforms were densified by thermal gradient chemical vapor infiltration. Results indicated that, although the linear and mass ablation rates exhibited by the HfC-C/C composites were lower than those for the C/C composites by 55% and 21%, respectively, the maximum flexural load for the C/C composites was significantly higher by 33% than that of HfC-C/C composites. The influence of pre-impact loading on mechanical behavior was greater for the HfC-C/C composites than for the C/C composites.

  19. MODIS: an audio motif discovery software

    OpenAIRE

    Catanese, Laurence; Souviraà-Labastie, Nathan; Qu, Bingqing; Campion, Sébastien; Gravier, Guillaume; Vincent, Emmanuel; Bimbot, Frédéric

    2013-01-01

    International audience MODIS is a free speech and audio motif discovery software developed at IRISA Rennes. Motif discovery is the task of discovering and collecting occurrences of repeating patterns in the absence of prior knowledge, or training material. MODIS is based on a generic approach to mine repeating audio sequences, with tolerance to motif variability. The algorithm implementation allows to process large audio streams at a reasonable speed where motif discovery often requires hu...

  20. Structural Motifs of Gold Nanoparticles.

    Science.gov (United States)

    Cleveland, C. L.; Luedtke, W. D.; Landman, Uzi

    1996-03-01

    Through an extensive search, involving energy minimization using embedded atom potentials, we found(R.L. Whetten et al./), submitted to Nature (1995). that the energetically optimal sequence for AuN clusters (30 motif, and variants thereof. These predictions for bare gold particles, and for particles coated by sef-assembled thiol monolayers, are discussed in light of recent experiments on the preparation and characterization (including mass spectrometry, electron microscopy, and X-ray diffraction) of nanocrystalline gold molecules (see Ref. 2).

  1. Main: TCA1MOTIF [PLACE

    Lifescience Database Archive (English)

    Full Text Available TCA1MOTIF S000159 17-May-1998 (last modified) kehi TCA-1 (tobacco nuclear protein 1...) binding site; Related to salicylic acid-inducible expression of many genes; Found in barley beta-1,3-gluca...nase and over 30 different plant genes which are known to be induced by one or more forms of stress; A similar sequence (TCA... et al., 1997); SA; salicylic acid; stress; TCA-1; barley (Hordeum vulgare); tobacco (Nicotiana tabacum); TCATCTTCTT ...

  2. Characterization of C/C composites porosity for the fusion

    International Nuclear Information System (INIS)

    In tokamaks, the composites C/C are used as components facing the plasma because of their excellent thermo-mechanical properties. In Tore Supra tokamak, analysis of particles of graphite erosion showed a big deuterium retention by the machine wall. This fuel retention will lead in ITER to a non acceptable level of tritium. As the diffusion in materials is bound to the porosity, the authors realized a study of two composites porosity: N11 and NB31. Different analysis methods have been performed and the temperature or grain size dependence studied. (A.L.B.)

  3. Gentamicin binds to the megalin receptor as a competitive inhibitor using the common ligand binding motif of complement type repeats: insight from the nmr structure of the 10th complement type repeat domain alone and in complex with gentamicin

    NARCIS (Netherlands)

    Dagil, R.; O'Shea, C.; Nykjaer, A.; Bonvin, A.M.J.J.; Kragelund, B.B.

    2013-01-01

    Gentamicin is an aminoglycoside widely used in treatments of, in particular, enterococcal, mycobacterial, and severe Gram-negative bacterial infections. Large doses of gentamicin cause nephrotoxicity and ototoxicity, entering the cell via the receptor megalin. Until now, no structural information ha

  4. Identification of a novel immunoreceptor tyrosine-based activation motif-containing molecule, STAM2, by mass spectrometry and its involvement in growth factor and cytokine receptor signaling pathways

    DEFF Research Database (Denmark)

    Pandey, A; Fernandez, M M; Steen, H;

    2000-01-01

    In an effort to clone novel tyrosine-phosphorylated substrates of the epidermal growth factor receptor, we have initiated an approach coupling affinity purification using anti-phosphotyrosine antibodies to mass spectrometry-based identification. Here, we report the identification of a signaling m...

  5. Comprehensive discovery of DNA motifs in 349 human cells and tissues reveals new features of motifs.

    Science.gov (United States)

    Zheng, Yiyu; Li, Xiaoman; Hu, Haiyan

    2015-01-01

    Comprehensive motif discovery under experimental conditions is critical for the global understanding of gene regulation. To generate a nearly complete list of human DNA motifs under given conditions, we employed a novel approach to de novo discover significant co-occurring DNA motifs in 349 human DNase I hypersensitive site datasets. We predicted 845 to 1325 motifs in each dataset, for a total of 2684 non-redundant motifs. These 2684 motifs contained 54.02 to 75.95% of the known motifs in seven large collections including TRANSFAC. In each dataset, we also discovered 43 663 to 2 013 288 motif modules, groups of motifs with their binding sites co-occurring in a significant number of short DNA regions. Compared with known interacting transcription factors in eight resources, the predicted motif modules on average included 84.23% of known interacting motifs. We further showed new features of the predicted motifs, such as motifs enriched in proximal regions rarely overlapped with motifs enriched in distal regions, motifs enriched in 5' distal regions were often enriched in 3' distal regions, etc. Finally, we observed that the 2684 predicted motifs classified the cell or tissue types of the datasets with an accuracy of 81.29%. The resources generated in this study are available at http://server.cs.ucf.edu/predrem/.

  6. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  7. Motif Detection Inspired by Immune Memory

    CERN Document Server

    Wilson, William; Aickelin, Uwe

    2010-01-01

    The search for patterns or motifs in data represents an area of key interest to many researchers. In this paper we present the Motif Tracking Algorithm, a novel immune inspired pattern identification tool that is able to identify variable length unknown motifs which repeat within time series data. The algorithm searches from a completely neutral perspective that is independent of the data being analysed and the underlying motifs. In this paper we test the flexibility of the motif tracking algorithm by applying it to the search for patterns in two industrial data sets. The algorithm is able to identify a population of motifs successfully in both cases, and the value of these motifs is discussed.

  8. Measurements of $\\psi(3686) \\to K^{-} \\Lambda \\bar{\\Xi}^{+} +c.c.$ and $\\psi(3686) \\to \\gamma K^{-} \\Lambda \\bar{\\Xi}^{+} +c.c$

    CERN Document Server

    Ablikim, M; Ai, X C; Albayrak, O; Albrecht, M; Ambrose, D J; Amoroso, A; An, F F; An, Q; Bai, J Z; Ferroli, R Baldini; Ban, Y; Bennett, D W; Bennett, J V; Bertani, M; Bettoni, D; Bian, J M; Bianchi, F; Boger, E; Bondarenko, O; Boyko, I; Briere, R A; Cai, H; Cai, X; Cakir, O; Calcaterra, A; Cao, G F; Cetin, S A; Chang, J F; Chelkov, G; Chen, G; Chen, H S; Chen, H Y; Chen, J C; Chen, M L; Chen, S J; Chen, X; Chen, X R; Chen, Y B; Cheng, H P; Chu, X K; Cibinetto, G; Cronin-Hennessy, D; Dai, H L; Dai, J P; Dbeyssi, A; Dedovich, D; Deng, Z Y; Denig, A; Denysenko, I; Destefanis, M; DeMori, F; Ding, Y; Dong, C; Dong, J; Dong, L Y; Dong, M Y; Du, S X; Duan, P F; Fan, J Z; Fang, J; Fang, S S; Fang, X; Fang, Y; Fava, L; Feldbauer, F; Felici, G; Feng, C Q; Fioravanti, E; Fritsch, M; Fu, C D; Gao, Q; Gao, X Y; Gao, Y; Gao, Z; Garzia, I; Geng, C; Goetzen, K; Gong, W X; Gradl, W; Greco, M; Gu, M H; Gu, Y T; Guan, Y H; Guo, A Q; Guo, L B; Guo, Y; Guo, Y P; Haddadi, Z; Hafner, A; Han, S; Han, Y L; Hao, X Q; Harris, F A; He, K L; He, Z Y; Held, T; Heng, Y K; Hou, Z L; Hu, C; Hu, H M; Hu, J F; Hu, T; Hu, Y; Huang, G M; Huang, G S; Huang, H P; Huang, J S; Huang, X T; Huang, Y; Hussain, T; Ji, Q; Ji, Q P; Ji, X B; Ji, X L; Jiang, L L; Jiang, L W; Jiang, X S; Jiao, J B; Jiao, Z; Jin, D P; Jin, S; Johansson, T; Julin, A; Kalantar-Nayestanaki, N; Kang, X L; Kang, X S; Kavatsyuk, M; Ke, B C; Kliemt, R; Kloss, B; Kolcu, O B; Kopf, B; Kornicer, M; Kühn, W; Kupsc, A; Lai, W; Lange, J S; Lara, M; Larin, P; Leng, C; Li, C H; Li, Cheng; Li, D M; Li, F; Li, G; Li, H B; Li, J C; Li, Jin; Li, K; Li, Lei; Li, P R; Li, T; Li, W D; Li, W G; Li, X L; Li, X M; Li, X N; Li, X Q; Li, Z B; Liang, H; Liang, Y F; Liang, Y T; Liao, G R; Lin, D X; Liu, B J; Liu, C X; Liu, F H; Liu, Fang; Liu, Feng; Liu, H B; Liu, H H; Liu, H M; Liu, J; Liu, J P; Liu, J Y; Liu, K; Liu, K Y; Liu, L D; Liu, P L; Liu, Q; Liu, S B; Liu, X; Liu, X X; Liu, Y B; Liu, Z A; Liu, Zhiqiang; Liu, Zhiqing; Loehner, H; Lou, X C; Lu, H J; Lu, J G; Lu, R Q; Lu, Y; Lu, Y P; Luo, C L; Luo, M X; Luo, T; Luo, X L; Lv, M; Lyu, X R; Ma, F C; Ma, H L; Ma, L L; Ma, Q M; Ma, S; Ma, T; Ma, X N; Ma, X Y; Maas, F E; Maggiora, M; Malik, Q A; Mao, Y J; Mao, Z P; Marcello, S; Messchendorp, J G; Min, J; Min, T J; Mitchell, R E; Mo, X H; Mo, Y J; Morales, C Morales; Moriya, K; Muchnoi, N Yu; Muramatsu, H; Nefedov, Y; Nerling, F; Nikolaev, I B; Ning, Z; Nisar, S; Niu, S L; Niu, X Y; Olsen, S L; Ouyang, Q; Pacetti, S; Patteri, P; Pelizaeus, M; Peng, H P; Peters, K; Pettersson, J; Ping, J L; Ping, R G; Poling, R; Pu, Y N; Qi, M; Qian, S; Qiao, C F; Qin, L Q; Qin, N; Qin, X S; Qin, Y; Qin, Z H; Qiu, J F; Rashid, K H; Redmer, C F; Ren, H L; Ripka, M; Rong, G; Ruan, X D; Santoro, V; Sarantsev, A; Savrié, M; Schoenning, K; Schumann, S; Shan, W; Shao, M; Shen, C P; Shen, P X; Shen, X Y; Sheng, H Y; Song, W M; Song, X Y; Sosio, S; Spataro, S; Sun, G X; Sun, J F; Sun, S S; Sun, Y J; Sun, Y Z; Sun, Z J; Sun, Z T; Tang, C J; Tang, X; Tapan, I; Thorndike, E H; Tiemens, M; Toth, D; Ullrich, M; Uman, I; Varner, G S; Wang, B; Wang, B L; Wang, D; Wang, D Y; Wang, K; Wang, L L; Wang, L S; Wang, M; Wang, P; Wang, P L; Wang, Q J; Wang, S G; Wang, W; Wang, X F; Wang, Y D; Wang, Y F; Wang, Y Q; Wang, Z; Wang, Z G; Wang, Z H; Wang, Z Y; Weber, T; Wei, D H; Wei, J B; Weidenkaff, P; Wen, S P; Wiedner, U; Wolke, M; Wu, L H; Wu, Z; Xia, L G; Xia, Y; Xiao, D; Xiao, Z J; Xie, Y G; Xiu, Q L; Xu, G F; Xu, L; Xu, Q J; Xu, Q N; Xu, X P; Yan, L; Yan, W B; Yan, W C; Yan, Y H; Yang, H X; Yang, L; Yang, Y; Yang, Y X; Ye, H; Ye, M; Ye, M H; Yin, J H; Yu, B X; Yu, C X; Yu, H W; Yu, J S; Yuan, C Z; Yuan, W L; Yuan, Y; Yuncu, A; Zafar, A A; Zallo, A; Zeng, Y; Zhang, B X; Zhang, B Y; Zhang, C; Zhang, C C; Zhang, D H; Zhang, H H; Zhang, H Y; Zhang, J J; Zhang, J L; Zhang, J Q; Zhang, J W; Zhang, J Y; Zhang, J Z; Zhang, K; Zhang, L; Zhang, S H; Zhang, X Y; Zhang, Y; Zhang, Y H; Zhang, Y T; Zhang, Z H; Zhang, Z P; Zhang, Z Y; Zhao, G; Zhao, J W; Zhao, J Y; Zhao, J Z; Zhao, Lei; Zhao, Ling; Zhao, M G; Zhao, Q; Zhao, Q W; Zhao, S J; Zhao, T C; Zhao, Y B; Zhao, Z G; Zhemchugov, A; Zheng, B; Zheng, J P; Zheng, W J; Zheng, Y H; Zhong, B; Zhou, L; Zhou, Li; Zhou, X; Zhou, X K; Zhou, X R; Zhou, X Y; Zhu, K; Zhu, K J; Zhu, S; Zhu, X L; Zhu, Y C; Zhu, Y S; Zhu, Z A; Zhuang, J; Zotti, L; Zou, B S; Zou, J H

    2015-01-01

    Using a sample of $1.06\\times10^8\\ \\psip$ events produced in $e^+e^-$ collisions at $\\sqrt{s}$ = 3.686 GeV and collected with the BESIII detector at the BEPCII collider, we present studies of the decays $\\klx+c.c.$ and $\\gklx+c.c.$. We observe two hyperons, $\\Xi(1690)^-$ and $\\Xi(1820)^-$, in the $K^-\\Lambda$ invariant mass distribution in the decay $\\klx+c.c.$ with significances of $4.9 \\sigma$ and $6.2 \\sigma$, respectively. The branching fractions of $\\klx+c.c.$, $\\ksx+c.c.$, $\\psip\\to\\gamma \\chi_{cJ}\\to \\gamma K^- \\Lambda \\bar{\\Xi}^+ +c.c.$ $(J=0,\\ 1,\\ 2)$, and $\\psip\\to \\Xi(1690/1820)^{-} \\bar{\\Xi}^++c.c$ with subsequent decay $\\Xi(1690/1820)^-\\to K^-\\Lambda$ are measured for the first time.

  9. Rapid chemical vapor infiltration of C/C composites

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ming-yu; WANG Li-ping; HUANG Qi-zhong; CHAI Li-yuan

    2009-01-01

    With liquid petrol gas (LPG) as carbon source,carbon felt as porous perform and hydrogen as diluent,C/C composites were fast fabricated by using a multi-physics field chemical vapor infiltration (MFCVI) process in a self-made furnace.A set of orthogonal experiments were carried out to optimize parameters in terms of indices of density and graphitization degree.The results show the optimal indices can be achieved under the conditions of temperature 650 ℃,LPG concentration 80%,gas flux 60 mL/s,total pressure 20 kPa,infiltration time 15 h.The verification experiment proves the effectiveness of the orthogonal experiments.Under the optimal conditions,the graphitization degree of 75% and bulk density of 1.69 g/cm are achieved with a uniform density distribution.At the same time,a new structure is obtained.

  10. Discovering sequence motifs in quantitative and qualitative pepetide data

    DEFF Research Database (Denmark)

    Andreatta, Massimo

    and interpret such data. The first paper in this thesis presents a new, publicly available method based on artificial neural networks that allows custom analysis of quantitative peptide data. The online NNAlign web-server provides a simple yet powerful tool for the discovery of sequence motifs in large...... of interactions in a single experiment, with virtually unlimited choice of potential targets and variants of these targets. However, the amount and complexity of data produced by high-throughput techniques poses serious challenges to researchers of limited bioinformatics expertise who need to analyze...... with the presence of multiple motifs, due to the experimental setup or the actual poly-specificity of the receptor, in peptide data. A new algorithm, based on Gibbs sampling, identifies multiple specificities by performing two tasks simultaneously: alignment and clustering of peptide data. The method, available...

  11. Statistical tests to compare motif count exceptionalities

    Directory of Open Access Journals (Sweden)

    Vandewalle Vincent

    2007-03-01

    Full Text Available Abstract Background Finding over- or under-represented motifs in biological sequences is now a common task in genomics. Thanks to p-value calculation for motif counts, exceptional motifs are identified and represent candidate functional motifs. The present work addresses the related question of comparing the exceptionality of one motif in two different sequences. Just comparing the motif count p-values in each sequence is indeed not sufficient to decide if this motif is significantly more exceptional in one sequence compared to the other one. A statistical test is required. Results We develop and analyze two statistical tests, an exact binomial one and an asymptotic likelihood ratio test, to decide whether the exceptionality of a given motif is equivalent or significantly different in two sequences of interest. For that purpose, motif occurrences are modeled by Poisson processes, with a special care for overlapping motifs. Both tests can take the sequence compositions into account. As an illustration, we compare the octamer exceptionalities in the Escherichia coli K-12 backbone versus variable strain-specific loops. Conclusion The exact binomial test is particularly adapted for small counts. For large counts, we advise to use the likelihood ratio test which is asymptotic but strongly correlated with the exact binomial test and very simple to use.

  12. An Algorithm for Motif Discovery with Iteration on Lengths of Motifs.

    Science.gov (United States)

    Fan, Yetian; Wu, Wei; Yang, Jie; Yang, Wenyu; Liu, Rongrong

    2015-01-01

    Analysis of DNA sequence motifs is becoming increasingly important in the study of gene regulation, and the identification of motif in DNA sequences is a complex problem in computational biology. Motif discovery has attracted the attention of more and more researchers, and varieties of algorithms have been proposed. Most existing motif discovery algorithms fix the motif's length as one of the input parameters. In this paper, a novel method is proposed to identify the optimal length of the motif and the optimal motif with that length, through an iteration process on increasing length numbers. For each fixed length, a modified genetic algorithm (GA) is used for finding the optimal motif with that length. Three operators are used in the modified GA: Mutation that is similar to the one used in usual GA but is modified to avoid local optimum in our case, and Addition and Deletion that are proposed by us for the problem. A criterion is given for singling out the optimal length in the increasing motif's lengths. We call this method AMDILM (an algorithm for motif discovery with iteration on lengths of motifs). The experiments on simulated data and real biological data show that AMDILM can accurately identify the optimal motif length. Meanwhile, the optimal motifs discovered by AMDILM are consistent with the real ones and are similar with the motifs obtained by the three well-known methods: Gibbs Sampler, MEME and Weeder. PMID:26357084

  13. Predicting conserved protein motifs with Sub-HMMs

    Directory of Open Access Journals (Sweden)

    Girke Thomas

    2010-04-01

    Full Text Available Abstract Background Profile HMMs (hidden Markov models provide effective methods for modeling the conserved regions of protein families. A limitation of the resulting domain models is the difficulty to pinpoint their much shorter functional sub-features, such as catalytically relevant sequence motifs in enzymes or ligand binding signatures of receptor proteins. Results To identify these conserved motifs efficiently, we propose a method for extracting the most information-rich regions in protein families from their profile HMMs. The method was used here to predict a comprehensive set of sub-HMMs from the Pfam domain database. Cross-validations with the PROSITE and CSA databases confirmed the efficiency of the method in predicting most of the known functionally relevant motifs and residues. At the same time, 46,768 novel conserved regions could be predicted. The data set also allowed us to link at least 461 Pfam domains of known and unknown function by their common sub-HMMs. Finally, the sub-HMM method showed very promising results as an alternative search method for identifying proteins that share only short sequence similarities. Conclusions Sub-HMMs extend the application spectrum of profile HMMs to motif discovery. Their most interesting utility is the identification of the functionally relevant residues in proteins of known and unknown function. Additionally, sub-HMMs can be used for highly localized sequence similarity searches that focus on shorter conserved features rather than entire domains or global similarities. The motif data generated by this study is a valuable knowledge resource for characterizing protein functions in the future.

  14. rMotifGen: random motif generator for DNA and protein sequences

    Directory of Open Access Journals (Sweden)

    Hardin C Timothy

    2007-08-01

    Full Text Available Abstract Background Detection of short, subtle conserved motif regions within a set of related DNA or amino acid sequences can lead to discoveries about important regulatory domains such as transcription factor and DNA binding sites as well as conserved protein domains. In order to help assess motif detection algorithms on motifs with varying properties and levels of conservation, we have developed a computational tool, rMotifGen, with the sole purpose of generating a number of random DNA or protein sequences containing short sequence motifs. Each motif consensus can be user-defined, randomly generated, or created from a position-specific scoring matrix (PSSM. Insertions and mutations within these motifs are created according to user-defined parameters and substitution matrices. The resulting sequences can be helpful in mutational simulations and in testing the limits of motif detection algorithms. Results Two implementations of rMotifGen have been created, one providing a graphical user interface (GUI for random motif construction, and the other serving as a command line interface. The second implementation has the added advantages of platform independence and being able to be called in a batch mode. rMotifGen was used to construct sample sets of sequences containing DNA motifs and amino acid motifs that were then tested against the Gibbs sampler and MEME packages. Conclusion rMotifGen provides an efficient and convenient method for creating random DNA or amino acid sequences with a variable number of motifs, where the instance of each motif can be incorporated using a position-specific scoring matrix (PSSM or by creating an instance mutated from its corresponding consensus using an evolutionary model based on substitution matrices. rMotifGen is freely available at: http://bioinformatics.louisville.edu/brg/rMotifGen/.

  15. Exon silencing by UAGG motifs in response to neuronal excitation.

    Directory of Open Access Journals (Sweden)

    Ping An

    2007-02-01

    Full Text Available Alternative pre-mRNA splicing plays fundamental roles in neurons by generating functional diversity in proteins associated with the communication and connectivity of the synapse. The CI cassette of the NMDA R1 receptor is one of a variety of exons that show an increase in exon skipping in response to cell excitation, but the molecular nature of this splicing responsiveness is not yet understood. Here we investigate the molecular basis for the induced changes in splicing of the CI cassette exon in primary rat cortical cultures in response to KCl-induced depolarization using an expression assay with a tight neuron-specific readout. In this system, exon silencing in response to neuronal excitation was mediated by multiple UAGG-type silencing motifs, and transfer of the motifs to a constitutive exon conferred a similar responsiveness by gain of function. Biochemical analysis of protein binding to UAGG motifs in extracts prepared from treated and mock-treated cortical cultures showed an increase in nuclear hnRNP A1-RNA binding activity in parallel with excitation. Evidence for the role of the NMDA receptor and calcium signaling in the induced splicing response was shown by the use of specific antagonists, as well as cell-permeable inhibitors of signaling pathways. Finally, a wider role for exon-skipping responsiveness is shown to involve additional exons with UAGG-related silencing motifs, and transcripts involved in synaptic functions. These results suggest that, at the post-transcriptional level, excitable exons such as the CI cassette may be involved in strategies by which neurons mount adaptive responses to hyperstimulation.

  16. Biological network motif detection: principles and practice.

    Science.gov (United States)

    Wong, Elisabeth; Baur, Brittany; Quader, Saad; Huang, Chun-Hsi

    2012-03-01

    Network motifs are statistically overrepresented sub-structures (sub-graphs) in a network, and have been recognized as 'the simple building blocks of complex networks'. Study of biological network motifs may reveal answers to many important biological questions. The main difficulty in detecting larger network motifs in biological networks lies in the facts that the number of possible sub-graphs increases exponentially with the network or motif size (node counts, in general), and that no known polynomial-time algorithm exists in deciding if two graphs are topologically equivalent. This article discusses the biological significance of network motifs, the motivation behind solving the motif-finding problem, and strategies to solve the various aspects of this problem. A simple classification scheme is designed to analyze the strengths and weaknesses of several existing algorithms. Experimental results derived from a few comparative studies in the literature are discussed, with conclusions that lead to future research directions. PMID:22396487

  17. Electron interactions with c-C4F8

    International Nuclear Information System (INIS)

    The limited electron collision cross-section and transport-coefficient data for the plasma processing gas perfluorocyclobutane (c-C4F8) are synthesized, assessed, and discussed. These include cross sections for total electron scattering, differential elastic electron scattering, partial and total ionization, dissociation into neutral fragments, and electron attachment, as well as data on electron transport, ionization, and attachment coefficients. The available data on both the electron collision cross sections and the electron transport coefficients require confirmation. Also, measurements are needed of the momentum transfer and elastic integral cross sections, and of the cross sections for other significant low-energy electron collision processes such as vibrational and electronic excitation. In addition, electron transport data over a wider range of values of the density-reduced electric field are needed. The present assessment of data on electron affinity, attachment, and scattering suggests the existence of negative ion states near -0.6, 4.9, 6.9, 9.0, and 10.5 eV

  18. PairMotif: A New Pattern-Driven Algorithm for Planted (l, d) DNA Motif Search

    OpenAIRE

    Qiang Yu; Hongwei Huo; Yipu Zhang; Hongzhi Guo

    2012-01-01

    Motif search is a fundamental problem in bioinformatics with an important application in locating transcription factor binding sites (TFBSs) in DNA sequences. The exact algorithms can report all (l, d) motifs and find the best one under a specific objective function. However, it is still a challenging task to identify weak motifs, since either a large amount of memory or execution time is required by current exact algorithms. A new exact algorithm, PairMotif, is proposed for planted (l, d) mo...

  19. Assessment of composite motif discovery methods

    Directory of Open Access Journals (Sweden)

    Johansen Jostein

    2008-02-01

    Full Text Available Abstract Background Computational discovery of regulatory elements is an important area of bioinformatics research and more than a hundred motif discovery methods have been published. Traditionally, most of these methods have addressed the problem of single motif discovery – discovering binding motifs for individual transcription factors. In higher organisms, however, transcription factors usually act in combination with nearby bound factors to induce specific regulatory behaviours. Hence, recent focus has shifted from single motifs to the discovery of sets of motifs bound by multiple cooperating transcription factors, so called composite motifs or cis-regulatory modules. Given the large number and diversity of methods available, independent assessment of methods becomes important. Although there have been several benchmark studies of single motif discovery, no similar studies have previously been conducted concerning composite motif discovery. Results We have developed a benchmarking framework for composite motif discovery and used it to evaluate the performance of eight published module discovery tools. Benchmark datasets were constructed based on real genomic sequences containing experimentally verified regulatory modules, and the module discovery programs were asked to predict both the locations of these modules and to specify the single motifs involved. To aid the programs in their search, we provided position weight matrices corresponding to the binding motifs of the transcription factors involved. In addition, selections of decoy matrices were mixed with the genuine matrices on one dataset to test the response of programs to varying levels of noise. Conclusion Although some of the methods tested tended to score somewhat better than others overall, there were still large variations between individual datasets and no single method performed consistently better than the rest in all situations. The variation in performance on individual

  20. MSDmotif: exploring protein sites and motifs

    Directory of Open Access Journals (Sweden)

    Henrick Kim

    2008-07-01

    Full Text Available Abstract Background Protein structures have conserved features – motifs, which have a sufficient influence on the protein function. These motifs can be found in sequence as well as in 3D space. Understanding of these fragments is essential for 3D structure prediction, modelling and drug-design. The Protein Data Bank (PDB is the source of this information however present search tools have limited 3D options to integrate protein sequence with its 3D structure. Results We describe here a web application for querying the PDB for ligands, binding sites, small 3D structural and sequence motifs and the underlying database. Novel algorithms for chemical fragments, 3D motifs, ϕ/ψ sequences, super-secondary structure motifs and for small 3D structural motif associations searches are incorporated. The interface provides functionality for visualization, search criteria creation, sequence and 3D multiple alignment options. MSDmotif is an integrated system where a results page is also a search form. A set of motif statistics is available for analysis. This set includes molecule and motif binding statistics, distribution of motif sequences, occurrence of an amino-acid within a motif, correlation of amino-acids side-chain charges within a motif and Ramachandran plots for each residue. The binding statistics are presented in association with properties that include a ligand fragment library. Access is also provided through the distributed Annotation System (DAS protocol. An additional entry point facilitates XML requests with XML responses. Conclusion MSDmotif is unique by combining chemical, sequence and 3D data in a single search engine with a range of search and visualisation options. It provides multiple views of data found in the PDB archive for exploring protein structures.

  1. Oxidation Behavior of C/C-SiC Gradient Matrix Composites

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Oxidation behavior of C/C-SiC gradient matrix composites and C/C composites were compared in stationary air. The results show that oxidation threshold of C-SiC materials increases with the amount of SiC particles in the codeposition matrix. Oxidation rate of C/C-SiC gradient matrix composites is significantly lower than that of C/C material. The micro-oxidation process was observed by SEM.

  2. Rh(III)-Catalyzed C-C/C-N Coupling of Imidates with α-Diazo Imidamide: Synthesis of Isoquinoline-Fused Indoles.

    Science.gov (United States)

    Wang, He; Li, Lei; Yu, Songjie; Li, Yunyun; Li, Xingwei

    2016-06-17

    Imidate esters and diazo compounds have been established as bifunctional substrates for the construction of biologically active fused heterocycles via rhodium-catalyzed C-H activation and C-C/C-N coupling. This reaction occurs under mild conditions with high efficiency, step economy, and low catalyst loading. PMID:27280947

  3. The Novel Selective Reduction of the C-C Triple Bond

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A novel reduction system is reported here in which the compounds with terminal C-C triple bond and disubstituted C-C triple bond react with NaBH4/Pd(PPh3)4 in a base condition and only terminal C-C triple bond is reduced.

  4. Helix-packing motifs in membrane proteins.

    Science.gov (United States)

    Walters, R F S; DeGrado, W F

    2006-09-12

    The fold of a helical membrane protein is largely determined by interactions between membrane-imbedded helices. To elucidate recurring helix-helix interaction motifs, we dissected the crystallographic structures of membrane proteins into a library of interacting helical pairs. The pairs were clustered according to their three-dimensional similarity (rmsd universe of common transmembrane helix-pairing motifs is relatively simple. The largest cluster, which comprises 29% of the library members, consists of an antiparallel motif with left-handed packing angles, and it is frequently stabilized by packing of small side chains occurring every seven residues in the sequence. Right-handed parallel and antiparallel structures show a similar tendency to segregate small residues to the helix-helix interface but spaced at four-residue intervals. Position-specific sequence propensities were derived for the most populated motifs. These structural and sequential motifs should be quite useful for the design and structural prediction of membrane proteins.

  5. Temporal motifs in time-dependent networks

    International Nuclear Information System (INIS)

    Temporal networks are commonly used to represent systems where connections between elements are active only for restricted periods of time, such as telecommunication, neural signal processing, biochemical reaction and human social interaction networks. We introduce the framework of temporal motifs to study the mesoscale topological–temporal structure of temporal networks in which the events of nodes do not overlap in time. Temporal motifs are classes of similar event sequences, where the similarity refers not only to topology but also to the temporal order of the events. We provide a mapping from event sequences to coloured directed graphs that enables an efficient algorithm for identifying temporal motifs. We discuss some aspects of temporal motifs, including causality and null models, and present basic statistics of temporal motifs in a large mobile call network

  6. A combinatorial code for splicing silencing: UAGG and GGGG motifs.

    Directory of Open Access Journals (Sweden)

    Kyoungha Han

    2005-05-01

    Full Text Available Alternative pre-mRNA splicing is widely used to regulate gene expression by tuning the levels of tissue-specific mRNA isoforms. Few regulatory mechanisms are understood at the level of combinatorial control despite numerous sequences, distinct from splice sites, that have been shown to play roles in splicing enhancement or silencing. Here we use molecular approaches to identify a ternary combination of exonic UAGG and 5'-splice-site-proximal GGGG motifs that functions cooperatively to silence the brain-region-specific CI cassette exon (exon 19 of the glutamate NMDA R1 receptor (GRIN1 transcript. Disruption of three components of the motif pattern converted the CI cassette into a constitutive exon, while predominant skipping was conferred when the same components were introduced, de novo, into a heterologous constitutive exon. Predominant exon silencing was directed by the motif pattern in the presence of six competing exonic splicing enhancers, and this effect was retained after systematically repositioning the two exonic UAGGs within the CI cassette. In this system, hnRNP A1 was shown to mediate silencing while hnRNP H antagonized silencing. Genome-wide computational analysis combined with RT-PCR testing showed that a class of skipped human and mouse exons can be identified by searches that preserve the sequence and spatial configuration of the UAGG and GGGG motifs. This analysis suggests that the multi-component silencing code may play an important role in the tissue-specific regulation of the CI cassette exon, and that it may serve more generally as a molecular language to allow for intricate adjustments and the coordination of splicing patterns from different genes.

  7. MotifLab: a tools and data integration workbench for motif discovery and regulatory sequence analysis

    Directory of Open Access Journals (Sweden)

    Klepper Kjetil

    2013-01-01

    Full Text Available Abstract Background Traditional methods for computational motif discovery often suffer from poor performance. In particular, methods that search for sequence matches to known binding motifs tend to predict many non-functional binding sites because they fail to take into consideration the biological state of the cell. In recent years, genome-wide studies have generated a lot of data that has the potential to improve our ability to identify functional motifs and binding sites, such as information about chromatin accessibility and epigenetic states in different cell types. However, it is not always trivial to make use of this data in combination with existing motif discovery tools, especially for researchers who are not skilled in bioinformatics programming. Results Here we present MotifLab, a general workbench for analysing regulatory sequence regions and discovering transcription factor binding sites and cis-regulatory modules. MotifLab supports comprehensive motif discovery and analysis by allowing users to integrate several popular motif discovery tools as well as different kinds of additional information, including phylogenetic conservation, epigenetic marks, DNase hypersensitive sites, ChIP-Seq data, positional binding preferences of transcription factors, transcription factor interactions and gene expression. MotifLab offers several data-processing operations that can be used to create, manipulate and analyse data objects, and complete analysis workflows can be constructed and automatically executed within MotifLab, including graphical presentation of the results. Conclusions We have developed MotifLab as a flexible workbench for motif analysis in a genomic context. The flexibility and effectiveness of this workbench has been demonstrated on selected test cases, in particular two previously published benchmark data sets for single motifs and modules, and a realistic example of genes responding to treatment with forskolin. MotifLab is freely

  8. Detecting Motifs in System Call Sequences

    CERN Document Server

    Wilson, William O; Aickelin, Uwe

    2010-01-01

    The search for patterns or motifs in data represents an area of key interest to many researchers. In this paper we present the Motif Tracking Algorithm, a novel immune inspired pattern identification tool that is able to identify unknown motifs which repeat within time series data. The power of the algorithm is derived from its use of a small number of parameters with minimal assumptions. The algorithm searches from a completely neutral perspective that is independent of the data being analysed, and the underlying motifs. In this paper the motif tracking algorithm is applied to the search for patterns within sequences of low level system calls between the Linux kernel and the operating system's user space. The MTA is able to compress data found in large system call data sets to a limited number of motifs which summarise that data. The motifs provide a resource from which a profile of executed processes can be built. The potential for these profiles and new implications for security research are highlighted. A...

  9. Automated motif discovery from glycan array data.

    Science.gov (United States)

    Cholleti, Sharath R; Agravat, Sanjay; Morris, Tim; Saltz, Joel H; Song, Xuezheng; Cummings, Richard D; Smith, David F

    2012-10-01

    Assessing interactions of a glycan-binding protein (GBP) or lectin with glycans on a microarray generates large datasets, making it difficult to identify a glycan structural motif or determinant associated with the highest apparent binding strength of the GBP. We have developed a computational method, termed GlycanMotifMiner, that uses the relative binding of a GBP with glycans within a glycan microarray to automatically reveal the glycan structural motifs recognized by a GBP. We implemented the software with a web-based graphical interface for users to explore and visualize the discovered motifs. The utility of GlycanMotifMiner was determined using five plant lectins, SNA, HPA, PNA, Con A, and UEA-I. Data from the analyses of the lectins at different protein concentrations were processed to rank the glycans based on their relative binding strengths. The motifs, defined as glycan substructures that exist in a large number of the bound glycans and few non-bound glycans, were then discovered by our algorithm and displayed in a web-based graphical user interface ( http://glycanmotifminer.emory.edu ). The information is used in defining the glycan-binding specificity of GBPs. The results were compared to the known glycan specificities of these lectins generated by manual methods. A more complex analysis was also carried out using glycan microarray data obtained for a recombinant form of human galectin-8. Results for all of these lectins show that GlycanMotifMiner identified the major motifs known in the literature along with some unexpected novel binding motifs. PMID:22877213

  10. Fitness for synchronization of network motifs

    DEFF Research Database (Denmark)

    Vega, Y.M.; Vázquez-Prada, M.; Pacheco, A.F.;

    2004-01-01

    We study the synchronization of Kuramoto's oscillators in small parts of networks known as motifs. We first report on the system dynamics for the case of a scale-free network and show the existence of a non-trivial critical point. We compute the probability that network motifs synchronize, and fi...... that the fitness for synchronization correlates well with motifs interconnectedness and structural complexity. Possible implications for present debates about network evolution in biological and other systems are discussed. © 2004 Elsevier B.V. All rights reserved....

  11. Correlating novel variable and conserved motifs in the Hemagglutinin protein with significant biological functions

    Directory of Open Access Journals (Sweden)

    Werner Mark

    2008-08-01

    Full Text Available Abstract Background Variations in the influenza Hemagglutinin protein contributes to antigenic drift resulting in decreased efficiency of seasonal influenza vaccines and escape from host immune response. We performed an in silico study to determine characteristics of novel variable and conserved motifs in the Hemagglutinin protein from previously reported H3N2 strains isolated from Hong Kong from 1968–1999 to predict viral motifs involved in significant biological functions. Results 14 MEME blocks were generated and comparative analysis of the MEME blocks identified blocks 1, 2, 3 and 7 to correlate with several biological functions. Analysis of the different Hemagglutinin sequences elucidated that the single block 7 has the highest frequency of amino acid substitution and the highest number of co-mutating pairs. MEME 2 showed intermediate variability and MEME 1 was the most conserved. Interestingly, MEME blocks 2 and 7 had the highest incidence of potential post-translational modifications sites including phosphorylation sites, ASN glycosylation motifs and N-myristylation sites. Similarly, these 2 blocks overlap with previously identified antigenic sites and receptor binding sites. Conclusion Our study identifies motifs in the Hemagglutinin protein with different amino acid substitution frequencies over a 31 years period, and derives relevant functional characteristics by correlation of these motifs with potential post-translational modifications sites, antigenic and receptor binding sites.

  12. Creation of Hybrid Nanorods From Sequences of Natural Trimeric Fibrous Proteins Using the Fibritin Trimerization Motif

    Science.gov (United States)

    Papanikolopoulou, Katerina; van Raaij, Mark J.; Mitraki, Anna

    Stable, artificial fibrous proteins that can be functionalized open new avenues in fields such as bionanomaterials design and fiber engineering. An important source of inspiration for the creation of such proteins are natural fibrous proteins such as collagen, elastin, insect silks, and fibers from phages and viruses. The fibrous parts of this last class of proteins usually adopt trimeric, β-stranded structural folds and are appended to globular, receptor-binding domains. It has been recently shown that the globular domains are essential for correct folding and trimerization and can be successfully substituted by a very small (27-amino acid) trimerization motif from phage T4 fibritin. The hybrid proteins are correctly folded nanorods that can withstand extreme conditions. When the fibrous part derives from the adenovirus fiber shaft, different tissue-targeting specificities can be engineered into the hybrid proteins, which therefore can be used as gene therapy vectors. The integration of such stable nanorods in devices is also a big challenge in the field of biomechanical design. The fibritin foldon domain is a versatile trimerization motif and can be combined with a variety of fibrous motifs, such as coiled-coil, collagenous, and triple β-stranded motifs, provided the appropriate linkers are used. The combination of different motifs within the same fibrous molecule to create stable rods with multiple functions can even be envisioned. We provide a comprehensive overview of the experimental procedures used for designing, creating, and characterizing hybrid fibrous nanorods using the fibritin trimerization motif.

  13. MotifMiner: A Table Driven Greedy Algorithm for DNA Motif Mining

    Science.gov (United States)

    Seeja, K. R.; Alam, M. A.; Jain, S. K.

    DNA motif discovery is a much explored problem in functional genomics. This paper describes a table driven greedy algorithm for discovering regulatory motifs in the promoter sequences of co-expressed genes. The proposed algorithm searches both DNA strands for the common patterns or motifs. The inputs to the algorithm are set of promoter sequences, the motif length and minimum Information Content. The algorithm generates subsequences of given length from the shortest input promoter sequence. It stores these subsequences and their reverse complements in a table. Then it searches the remaining sequences for good matches of these subsequences. The Information Content score is used to measure the goodness of the motifs. The algorithm has been tested with synthetic data and real data. The results are found promising. The algorithm could discover meaningful motifs from the muscle specific regulatory sequences.

  14. Detecting seeded motifs in DNA sequences

    OpenAIRE

    Pizzi, Cinzia; Bortoluzzi, Stefania; Bisognin, Andrea; Coppe, Alessandro; Danieli, Gian Antonio

    2005-01-01

    The problem of detecting DNA motifs with functional relevance in real biological sequences is difficult due to a number of biological, statistical and computational issues and also because of the lack of knowledge about the structure of searched patterns. Many algorithms are implemented in fully automated processes, which are often based upon a guess of input parameters from the user at the very first step. In this paper, we present a novel method for the detection of seeded DNA motifs, compo...

  15. Structure and mechanical characterization of DNA i-motif nanowires by molecular dynamics simulation

    CERN Document Server

    Singh, Raghvendra Pratap; Cleri, Fabrizio

    2013-01-01

    We studied the structure and mechanical properties of DNA i-motif nanowires by means of molecular dynamics computer simulations. We built up to 230 nm long nanowires, based on a repeated TC5 sequence from crystallographic data, fully relaxed and equilibrated in water. The unusual stacked C*C+ stacked structure, formed by four ssDNA strands arranged in an intercalated tetramer, is here fully characterized both statically and dynamically. By applying stretching, compression and bending deformation with the steered molecular dynamics and umbrella sampling methods, we extract the apparent Young's and bending moduli of the nanowire, as wel as estimates for the tensile strength and persistence length. According to our results, the i-motif nanowire shares similarities with structural proteins, as far as its tensile stiffness, but is closer to nucleic acids and flexible proteins, as far as its bending rigidity is concerned. Furthermore, thanks to its very thin cross section, the apparent tensile toughness is close to...

  16. A survey of motif finding Web tools for detecting binding site motifs in ChIP-Seq data

    OpenAIRE

    Ngoc Tam L. Tran; Huang, Chun-Hsi

    2014-01-01

    Abstract ChIP-Seq (chromatin immunoprecipitation sequencing) has provided the advantage for finding motifs as ChIP-Seq experiments narrow down the motif finding to binding site locations. Recent motif finding tools facilitate the motif detection by providing user-friendly Web interface. In this work, we reviewed nine motif finding Web tools that are capable for detecting binding site motifs in ChIP-Seq data. We showed each motif finding Web tool has its own advantages for detecting motifs tha...

  17. Detecting seeded motifs in DNA sequences.

    Science.gov (United States)

    Pizzi, Cinzia; Bortoluzzi, Stefania; Bisognin, Andrea; Coppe, Alessandro; Danieli, Gian Antonio

    2005-01-01

    The problem of detecting DNA motifs with functional relevance in real biological sequences is difficult due to a number of biological, statistical and computational issues and also because of the lack of knowledge about the structure of searched patterns. Many algorithms are implemented in fully automated processes, which are often based upon a guess of input parameters from the user at the very first step. In this paper, we present a novel method for the detection of seeded DNA motifs, composed by regions with a different extent of variability. The method is based on a multi-step approach, which was implemented in a motif searching web tool (MOST). Overrepresented exact patterns are extracted from input sequences and clustered to produce motifs core regions, which are then extended and scored to generate seeded motifs. The combination of automated pattern discovery algorithms and different display tools for the evaluation and selection of results at several analysis steps can potentially lead to much more meaningful results than complete automation can produce. Experimental results on different yeast and human real datasets proved the methodology to be a promising solution for finding seeded motifs. MOST web tool is freely available at http://telethon.bio.unipd.it/bioinfo/MOST. PMID:16141193

  18. Chaotic motifs in gene regulatory networks.

    Science.gov (United States)

    Zhang, Zhaoyang; Ye, Weiming; Qian, Yu; Zheng, Zhigang; Huang, Xuhui; Hu, Gang

    2012-01-01

    Chaos should occur often in gene regulatory networks (GRNs) which have been widely described by nonlinear coupled ordinary differential equations, if their dimensions are no less than 3. It is therefore puzzling that chaos has never been reported in GRNs in nature and is also extremely rare in models of GRNs. On the other hand, the topic of motifs has attracted great attention in studying biological networks, and network motifs are suggested to be elementary building blocks that carry out some key functions in the network. In this paper, chaotic motifs (subnetworks with chaos) in GRNs are systematically investigated. The conclusion is that: (i) chaos can only appear through competitions between different oscillatory modes with rivaling intensities. Conditions required for chaotic GRNs are found to be very strict, which make chaotic GRNs extremely rare. (ii) Chaotic motifs are explored as the simplest few-node structures capable of producing chaos, and serve as the intrinsic source of chaos of random few-node GRNs. Several optimal motifs causing chaos with atypically high probability are figured out. (iii) Moreover, we discovered that a number of special oscillators can never produce chaos. These structures bring some advantages on rhythmic functions and may help us understand the robustness of diverse biological rhythms. (iv) The methods of dominant phase-advanced driving (DPAD) and DPAD time fraction are proposed to quantitatively identify chaotic motifs and to explain the origin of chaotic behaviors in GRNs.

  19. Detecting seeded motifs in DNA sequences

    Science.gov (United States)

    Pizzi, Cinzia; Bortoluzzi, Stefania; Bisognin, Andrea; Coppe, Alessandro; Danieli, Gian Antonio

    2005-01-01

    The problem of detecting DNA motifs with functional relevance in real biological sequences is difficult due to a number of biological, statistical and computational issues and also because of the lack of knowledge about the structure of searched patterns. Many algorithms are implemented in fully automated processes, which are often based upon a guess of input parameters from the user at the very first step. In this paper, we present a novel method for the detection of seeded DNA motifs, composed by regions with a different extent of variability. The method is based on a multi-step approach, which was implemented in a motif searching web tool (MOST). Overrepresented exact patterns are extracted from input sequences and clustered to produce motifs core regions, which are then extended and scored to generate seeded motifs. The combination of automated pattern discovery algorithms and different display tools for the evaluation and selection of results at several analysis steps can potentially lead to much more meaningful results than complete automation can produce. Experimental results on different yeast and human real datasets proved the methodology to be a promising solution for finding seeded motifs. MOST web tool is freely available at . PMID:16141193

  20. 3matrix and 3motif: a protein structure visualization system for conserved sequence motifs

    OpenAIRE

    Bennett, Steven P.; Lu, Lin; Brutlag, Douglas L.

    2003-01-01

    Computational methods such as sequence alignment and motif construction are useful in grouping related proteins into families, as well as helping to annotate new proteins of unknown function. These methods identify conserved amino acids in protein sequences, but cannot determine the specific functional or structural roles of conserved amino acids without additional study. In this work, we present 3matrix (http://3matrix.stanford.edu) and 3motif (http://3motif.stanford.edu), a web-based sequen...

  1. WebMOTIFS: automated discovery, filtering and scoring of DNA sequence motifs using multiple programs and Bayesian approaches.

    Science.gov (United States)

    Romer, Katherine A; Kayombya, Guy-Richard; Fraenkel, Ernest

    2007-07-01

    WebMOTIFS provides a web interface that facilitates the discovery and analysis of DNA-sequence motifs. Several studies have shown that the accuracy of motif discovery can be significantly improved by using multiple de novo motif discovery programs and using randomized control calculations to identify the most significant motifs or by using Bayesian approaches. WebMOTIFS makes it easy to apply these strategies. Using a single submission form, users can run several motif discovery programs and score, cluster and visualize the results. In addition, the Bayesian motif discovery program THEME can be used to determine the class of transcription factors that is most likely to regulate a set of sequences. Input can be provided as a list of gene or probe identifiers. Used with the default settings, WebMOTIFS accurately identifies biologically relevant motifs from diverse data in several species. WebMOTIFS is freely available at http://fraenkel.mit.edu/webmotifs.

  2. Andrographolide attenuates LPS-stimulated up-regulation of C-C and C-X-C motif chemokines in rodent cortex and primary astrocytes

    OpenAIRE

    Wong, Siew Ying; Tan, Michelle G.K.; Banks, William A.; Wong, W. S. Fred; Wong, Peter T.-H.; Lai, Mitchell K.P.

    2016-01-01

    Background Andrographolide is the major bioactive compound isolated from Andrographis paniculata, a native South Asian herb used medicinally for its anti-inflammatory properties. In this study, we aimed to assess andrographolide’s potential utility as an anti-neuroinflammatory therapeutic. Methods The effects of andrographolide on lipopolysaccharide (LPS)-induced chemokine up-regulation both in mouse cortex and in cultured primary astrocytes were measured, including cytokine profiling, gene e...

  3. Variants of C-C motif chemokine 22 (CCL22 are associated with susceptibility to atopic dermatitis: case-control studies.

    Directory of Open Access Journals (Sweden)

    Tomomitsu Hirota

    Full Text Available Atopic dermatitis (AD is a common inflammatory skin disease caused by multiple genetic and environmental factors. AD is characterized by the local infiltration of T helper type 2 (Th2 cells. Recent clinical studies have shown important roles of the Th2 chemokines, CCL22 and CCL17 in the pathogenesis of AD. To investigate whether polymorphisms of the CCL22 gene affect the susceptibility to AD, we conducted association studies and functional studies of the related variants. We first resequenced the CCL22 gene and found a total of 39 SNPs. We selected seven tag SNPs in the CCL22 gene, and conducted association studies using two independent Japanese populations (1(st population, 916 cases and 1,032 controls; 2(nd population 1,034 cases and 1,004 controls. After the association results were combined by inverse variance method, we observed a significant association at rs4359426 (meta-analysis, combined P = 9.6×10⁻⁶; OR, 0.74; 95% CI, 0.65-0.85. Functional analysis revealed that the risk allele of rs4359426 contributed to higher expression levels of CCL22 mRNA. We further examined the allelic differences in the binding of nuclear proteins by electrophoretic mobility shift assay. The signal intensity of the DNA-protein complex derived from the G allele of rs223821, which was in absolute LD with rs4359426, was higher than that from the A allele. Although further functional analyses are needed, it is likely that related variants play a role in susceptibility to AD in a gain-of-function manner. Our findings provide a new insight into the etiology and pathogenesis of AD.

  4. Variants of C-C motif chemokine 22 (CCL22) are associated with susceptibility to atopic dermatitis: case-control studies.

    Science.gov (United States)

    Hirota, Tomomitsu; Saeki, Hidehisa; Tomita, Kaori; Tanaka, Shota; Ebe, Kouji; Sakashita, Masafumi; Yamada, Takechiyo; Fujieda, Shigeharu; Miyatake, Akihiko; Doi, Satoru; Enomoto, Tadao; Hizawa, Nobuyuki; Sakamoto, Tohru; Masuko, Hironori; Sasaki, Takashi; Ebihara, Tamotsu; Amagai, Masayuki; Esaki, Hitokazu; Takeuchi, Satoshi; Furue, Masutaka; Noguchi, Emiko; Kamatani, Naoyuki; Nakamura, Yusuke; Kubo, Michiaki; Tamari, Mayumi

    2011-01-01

    Atopic dermatitis (AD) is a common inflammatory skin disease caused by multiple genetic and environmental factors. AD is characterized by the local infiltration of T helper type 2 (Th2) cells. Recent clinical studies have shown important roles of the Th2 chemokines, CCL22 and CCL17 in the pathogenesis of AD. To investigate whether polymorphisms of the CCL22 gene affect the susceptibility to AD, we conducted association studies and functional studies of the related variants. We first resequenced the CCL22 gene and found a total of 39 SNPs. We selected seven tag SNPs in the CCL22 gene, and conducted association studies using two independent Japanese populations (1(st) population, 916 cases and 1,032 controls; 2(nd) population 1,034 cases and 1,004 controls). After the association results were combined by inverse variance method, we observed a significant association at rs4359426 (meta-analysis, combined P = 9.6×10⁻⁶; OR, 0.74; 95% CI, 0.65-0.85). Functional analysis revealed that the risk allele of rs4359426 contributed to higher expression levels of CCL22 mRNA. We further examined the allelic differences in the binding of nuclear proteins by electrophoretic mobility shift assay. The signal intensity of the DNA-protein complex derived from the G allele of rs223821, which was in absolute LD with rs4359426, was higher than that from the A allele. Although further functional analyses are needed, it is likely that related variants play a role in susceptibility to AD in a gain-of-function manner. Our findings provide a new insight into the etiology and pathogenesis of AD.

  5. MOTIFATOR : detection and characterization of regulatory motifs using prokaryote transcriptome data

    NARCIS (Netherlands)

    Blom, Evert-Jan; Roerdink, Jos B.T.M.; Kuipers, Oscar P.; Hijum, Sacha A.F.T. van

    2009-01-01

    Unraveling regulatory mechanisms (e.g. identification of motifs in cis-regulatory regions) remains a major challenge in the analysis of transcriptome experiments. Existing applications identify putative motifs from gene lists obtained at rather arbitrary cutoff and require additional manual processi

  6. Sublinear Time Motif Discovery from Multiple Sequences

    Directory of Open Access Journals (Sweden)

    Yunhui Fu

    2013-10-01

    Full Text Available In this paper, a natural probabilistic model for motif discovery has been used to experimentally test the quality of motif discovery programs. In this model, there are k background sequences, and each character in a background sequence is a random character from an alphabet, Σ. A motif G = g1g2 ... gm is a string of m characters. In each background sequence is implanted a probabilistically-generated approximate copy of G. For a probabilistically-generated approximate copy b1b2 ... bm of G, every character, bi, is probabilistically generated, such that the probability for bi ≠ gi is at most α. We develop two new randomized algorithms and one new deterministic algorithm. They make advancements in the following aspects: (1 The algorithms are much faster than those before. Our algorithms can even run in sublinear time. (2 They can handle any motif pattern. (3 The restriction for the alphabet size is a lower bound of four. This gives them potential applications in practical problems, since gene sequences have an alphabet size of four. (4 All algorithms have rigorous proofs about their performances. The methods developed in this paper have been used in the software implementation. We observed some encouraging results that show improved performance for motif detection compared with other software.

  7. Functional characterization of variations on regulatory motifs.

    Directory of Open Access Journals (Sweden)

    Michal Lapidot

    2008-03-01

    Full Text Available Transcription factors (TFs regulate gene expression through specific interactions with short promoter elements. The same regulatory protein may recognize a variety of related sequences. Moreover, once they are detected it is hard to predict whether highly similar sequence motifs will be recognized by the same TF and regulate similar gene expression patterns, or serve as binding sites for distinct regulatory factors. We developed computational measures to assess the functional implications of variations on regulatory motifs and to compare the functions of related sites. We have developed computational means for estimating the functional outcome of substituting a single position within a binding site and applied them to a collection of putative regulatory motifs. We predict the effects of nucleotide variations within motifs on gene expression patterns. In cases where such predictions could be compared to suitable published experimental evidence, we found very good agreement. We further accumulated statistics from multiple substitutions across various binding sites in an attempt to deduce general properties that characterize nucleotide substitutions that are more likely to alter expression. We found that substitutions involving Adenine are more likely to retain the expression pattern and that substitutions involving Guanine are more likely to alter expression compared to the rest of the substitutions. Our results should facilitate the prediction of the expression outcomes of binding site variations. One typical important implication is expected to be the ability to predict the phenotypic effect of variation in regulatory motifs in promoters.

  8. 77 FR 10004 - C$ cMoney, Inc.; Order of Suspension of Trading

    Science.gov (United States)

    2012-02-21

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION C$ cMoney, Inc.; Order of Suspension of Trading February 16, 2012. It appears to the Securities... securities of C$ cMoney, Inc. (``cMoney'') because of questions regarding the accuracy of assertions by...

  9. Multielectron redox reactions involving C-C coupling and cleavage in uranium Schiff base complexes

    International Nuclear Information System (INIS)

    The reaction of U(III) with Schiff base ligands and the reduction of U(IV) Schiff base complexes both promote C-C bond formation to afford dinuclear or mononuclear U(IV) amido complexes, which can release up to four electrons to substrates through the oxidative cleavage of the C-C bond. (authors)

  10. Thermoelectric properties of SiC/C composites from wood charcoal by pulse current sintering

    NARCIS (Netherlands)

    Fujisawa, M; Hata, T; Bronsveld, P; Castro, [No Value; Tanaka, F; Kikuchi, H; Imamura, Y

    2005-01-01

    SiC/C composites were investigated by sintering a mix of wood charcoal and SiO2 powder (32-45 mu m) at 1400, 1600 and 1800 degrees C under N-2 atmosphere with a pulse current sintering method. Thermoelectric properties of SiC/C composites were investigated by measuring the Seebeck coefficient and th

  11. Testing of DLR C/C-SiC for HIFiRE 8 Scramjet Combustor

    Science.gov (United States)

    Glass, David E.; Capriotti, Diego P.; Reimer, Thomas; Kutemeyer, Marius; Smart, Michael

    2013-01-01

    Ceramic Matrix Composites (CMCs) have been proposed for hot structures in scramjet combustors. Previous studies have calculated significant weight savings by utilizing CMCs (active and passive) versus actively cooled metallic scramjet structures. Both a C/C and a C/C-SiC material system fabricated by DLR (Stuttgart, Germany) are being considered for use in a passively cooled combustor design for HIFiRE 8, a joint Australia / AFRL hypersonic flight program, expected to fly at Mach 7 for approximately 30 sec, at a dynamic pressure of 55 kPa. Flat panels of the DLR C/C and the C/C-SiC were tested in the NASA Langley Direct Connect Rig (DCR) at Mach 5 and Mach 6 enthalpy for several minutes. Gaseous hydrogen fuel was used to fuel the scramjet combustor. The test panels were instrumented with embedded Type K and Type S thermocouples. Zirconia felt insulation was used in some of the tests to increase the surface temperature of the C/C-SiC panel for approximately 350degF. The final C/C-SiC panel was tested for 3 cycles totaling over 135 sec at Mach 6 enthalpy. Slightly more erosion was observed on the C/C panel than the C/C-SiC panels, but both material systems demonstrated acceptable recession performance for the HIFiRE 8 flight.

  12. SMOTIF: efficient structured pattern and profile motif search

    OpenAIRE

    Zaki Mohammed J; Zhang Yongqiang

    2006-01-01

    Abstract Background A structured motif allows variable length gaps between several components, where each component is a simple motif, which allows either no gaps or only fixed length gaps. The motif can either be represented as a pattern or a profile (also called positional weight matrix). We propose an efficient algorithm, called SMOTIF, to solve the structured motif search problem, i.e., given one or more sequences and a structured motif, SMOTIF searches the sequences for all occurrences o...

  13. 在MATLAB环境下创建C/C++外部应用程序的方法%The Method of Establishing C/C++ Exterior Application under MATLAB

    Institute of Scientific and Technical Information of China (English)

    刘东华

    2000-01-01

    介绍了利用MATLAB编译器和MATLAB的C/C++Math函数库以及C/C++编译器生成C/C++应用程序的优点及具体的编译链接流程,并通过实例分析了创建C/C++应用程序的方法.

  14. Armadillo motifs involved in vesicular transport.

    Directory of Open Access Journals (Sweden)

    Harald Striegl

    Full Text Available Armadillo (ARM repeat proteins function in various cellular processes including vesicular transport and membrane tethering. They contain an imperfect repeating sequence motif that forms a conserved three-dimensional structure. Recently, structural and functional insight into tethering mediated by the ARM-repeat protein p115 has been provided. Here we describe the p115 ARM-motifs for reasons of clarity and nomenclature and show that both sequence and structure are highly conserved among ARM-repeat proteins. We argue that there is no need to invoke repeat types other than ARM repeats for a proper description of the structure of the p115 globular head region. Additionally, we propose to define a new subfamily of ARM-like proteins and show lack of evidence that the ARM motifs found in p115 are present in other long coiled-coil tethering factors of the golgin family.

  15. Sequential motif profile of natural visibility graphs

    CERN Document Server

    Iacovacci, Jacopo

    2016-01-01

    The concept of sequential visibility graph motifs -subgraphs appearing with characteristic frequencies in the visibility graphs associated to time series- has been advanced recently along with a theoretical framework to compute analytically the motif profiles associated to Horizontal Visibility Graphs (HVGs). Here we develop a theory to compute the profile of sequential visibility graph motifs in the context of Natural Visibility Graphs (VGs). This theory gives exact results for deterministic aperiodic processes with a smooth invariant density or stochastic processes that fulfil the Markov property and have a continuous marginal distribution. The framework also allows for a linear time numerical estimation in the case of empirical time series. A comparison between the HVG and the VG case (including evaluation of their robustness for short series polluted with measurement noise) is also presented.

  16. Effects of Hydrogen Ion Implantation on TiC-C Coating of Stainless Steel

    Institute of Scientific and Technical Information of China (English)

    ZHANG Rui-qian; LIU Yao-guang; HUANG Ning-kang

    2008-01-01

    Titanium carbide coatings are widely used as various wear-resistant material.The hydrogen erosion resistance of TiC-C films and the effect of hydrogen participation on TiC-C films were studied.Seventy-five percent TiC-C films are prepared on stainless steel surface by using ion mixing,where TiC-C films are deposited by rf magnetron sputtering followed by argon ion bombardment.The samples are then submitted to hydrogen ion implantation at 1.2×10-3 Pa.Characterization for the 75% TiC-C films was done with SIMS,XRD,AES,and XPS.Secondary ion mass spectroscopy (SIMS) was used to analyze hydrogen concentration variation with depth,X-Ray diffraction (XRD) was used to identify the phases,and Auger electron spectra (AES) as well as X-ray photoelectron spectra (XPS) were used to check the effects of hydrogen on shifts of chemical bonding states of C and Ti in the TiC-C films.It is found that TiC-C films on stainless steel surface can prevent hydrogen from entering stainless steel.

  17. Electron attachment properties of c-C4F8O in different environments

    Science.gov (United States)

    Chachereau, A.; Fedor, J.; Janečková, R.; Kočišek, J.; Rabie, M.; Franck, C. M.

    2016-09-01

    The electron attachment properties of octafluorotetrahydrofuran (c-C4F8O) are investigated using two complementary experimental setups. The attachment and ionization cross sections of c-C4F8O are measured using an electron beam experiment. The effective ionization rate coefficient, electron drift velocity and electron diffusion coefficient in c-C4F8O diluted to concentrations lower than 0.6% in the buffer gases N2, CO2 and Ar, are measured using a pulsed Townsend experiment. A kinetic model is proposed, which combines the results of the two experiments.

  18. Motifs and structural blocks retrieval by GHT

    Science.gov (United States)

    Cantoni, Virginio; Ferone, Alessio; Petrosino, Alfredo; Polat, Ozlem

    2014-06-01

    The structure of a protein gives more insight on the protein function than its amino acid sequence. Protein structure analysis and comparison are important for understanding the evolutionary relationships among proteins, predicting protein functions, and predicting protein folding. Proteins are formed by two basic regular 3D structural patterns, called Secondary Structures (SSs): helices and sheets. A structural motif is a compact 3D protein block referring to a small specific combination of secondary structural elements, which appears in a variety of molecules. In this paper we compare a few approaches for motif retrieval based on the Generalized Hough Transform (GHT). A primary technique is to adopt the single SS as structural primitives; alternatives are to adopt a SSs pair as primitive structural element, or a SSs triplet, and so on up-to an entire motif. The richer the primitive, the higher the time for pre-analysis and search, and the simpler the inspection process on the parameter space for analyzing the peaks. Performance comparisons, in terms of precision and computation time, are here presented considering the retrieval of motifs composed by three to five SSs for more than 15 million searches. The approach can be easily applied to the retrieval of greater blocks, up to protein domains, or even entire proteins.

  19. Highly scalable Ab initio genomic motif identification

    KAUST Repository

    Marchand, Benoît

    2011-01-01

    We present results of scaling an ab initio motif family identification system, Dragon Motif Finder (DMF), to 65,536 processor cores of IBM Blue Gene/P. DMF seeks groups of mutually similar polynucleotide patterns within a set of genomic sequences and builds various motif families from them. Such information is of relevance to many problems in life sciences. Prior attempts to scale such ab initio motif-finding algorithms achieved limited success. We solve the scalability issues using a combination of mixed-mode MPI-OpenMP parallel programming, master-slave work assignment, multi-level workload distribution, multi-level MPI collectives, and serial optimizations. While the scalability of our algorithm was excellent (94% parallel efficiency on 65,536 cores relative to 256 cores on a modest-size problem), the final speedup with respect to the original serial code exceeded 250,000 when serial optimizations are included. This enabled us to carry out many large-scale ab initio motiffinding simulations in a few hours while the original serial code would have needed decades of execution time. Copyright 2011 ACM.

  20. The Motif of Meeting in Digital Education

    Science.gov (United States)

    Sheail, Philippa

    2015-01-01

    This article draws on theoretical work which considers the composition of meetings, in order to think about the form of the meeting in digital environments for higher education. To explore the motif of meeting, I undertake a "compositional interpretation" (Rose, 2012) of the default interface offered by "Collaborate", an…

  1. Parallel motif extraction from very long sequences

    KAUST Repository

    Sahli, Majed

    2013-01-01

    Motifs are frequent patterns used to identify biological functionality in genomic sequences, periodicity in time series, or user trends in web logs. In contrast to a lot of existing work that focuses on collections of many short sequences, modern applications require mining of motifs in one very long sequence (i.e., in the order of several gigabytes). For this case, there exist statistical approaches that are fast but inaccurate; or combinatorial methods that are sound and complete. Unfortunately, existing combinatorial methods are serial and very slow. Consequently, they are limited to very short sequences (i.e., a few megabytes), small alphabets (typically 4 symbols for DNA sequences), and restricted types of motifs. This paper presents ACME, a combinatorial method for extracting motifs from a single very long sequence. ACME arranges the search space in contiguous blocks that take advantage of the cache hierarchy in modern architectures, and achieves almost an order of magnitude performance gain in serial execution. It also decomposes the search space in a smart way that allows scalability to thousands of processors with more than 90% speedup. ACME is the only method that: (i) scales to gigabyte-long sequences; (ii) handles large alphabets; (iii) supports interesting types of motifs with minimal additional cost; and (iv) is optimized for a variety of architectures such as multi-core systems, clusters in the cloud, and supercomputers. ACME reduces the extraction time for an exact-length query from 4 hours to 7 minutes on a typical workstation; handles 3 orders of magnitude longer sequences; and scales up to 16, 384 cores on a supercomputer. Copyright is held by the owner/author(s).

  2. DNA motif elucidation using belief propagation

    KAUST Repository

    Wong, Ka-Chun

    2013-06-29

    Protein-binding microarray (PBM) is a high-throughout platform that can measure the DNA-binding preference of a protein in a comprehensive and unbiased manner. A typical PBM experiment can measure binding signal intensities of a protein to all the possible DNA k-mers (k = 8 ?10); such comprehensive binding affinity data usually need to be reduced and represented as motif models before they can be further analyzed and applied. Since proteins can often bind to DNA in multiple modes, one of the major challenges is to decompose the comprehensive affinity data into multimodal motif representations. Here, we describe a new algorithm that uses Hidden Markov Models (HMMs) and can derive precise and multimodal motifs using belief propagations. We describe an HMM-based approach using belief propagations (kmerHMM), which accepts and preprocesses PBM probe raw data into median-binding intensities of individual k-mers. The k-mers are ranked and aligned for training an HMM as the underlying motif representation. Multiple motifs are then extracted from the HMM using belief propagations. Comparisons of kmerHMM with other leading methods on several data sets demonstrated its effectiveness and uniqueness. Especially, it achieved the best performance on more than half of the data sets. In addition, the multiple binding modes derived by kmerHMM are biologically meaningful and will be useful in interpreting other genome-wide data such as those generated from ChIP-seq. The executables and source codes are available at the authors\\' websites: e.g. http://www.cs.toronto.edu/?wkc/kmerHMM. 2013 The Author(s).

  3. Lightweight C&C based botnet detection using Aho-Corasick NFA

    Directory of Open Access Journals (Sweden)

    Udhayan J

    2010-10-01

    Full Text Available Botnet distinguishes itself from the previous malware by having the characteristics of a C&C channel,using which a Botmaster can control the constituents of the botnet. Even though protocols like IRC,HTTP and DNS are exploited to incorporate C&C channels, previous analysis have shown that themajority of the botnets are usually based on IRC. Consequently in this paper the Aho-Corasick NFAbased detection is proposed to detect the C&C instructions which is exchanged in IRC run botnets.However the ability to detect botnet is limited to the existing bot commands. Therefore a counting processwhich analyses every IRC messages is introduced to detect the existence of malicious codes. Thisdetection method and various existing methods have been evaluated using real-world network traces. Theresults show that the proposed C&C Instruction based IRC detection method can detect real-worldbotnets with high accuracy.

  4. C/C composite brake disk nondestructive evaluation by IR thermography

    Science.gov (United States)

    Chu, Tsuchin P.; Poudel, Anish; Filip, Peter

    2012-06-01

    This paper discusses the non-destructive evaluation of thick Carbon/Carbon (C/C) composite aircraft brake disks by using transient infrared thermography (IRT) approach. Thermal diffusivity measurement technique was applied to identify the subsurface anomalies in thick C/C brake disks. In addition, finite element analysis (FEA) modeling tool was used to determine the transient thermal response of the C/C disks that were subjected to flash heating. For this, series of finite element models were built and thermal responses with various thermal diffusivities subjected to different heating conditions were investigated. Experiments were conducted to verify the models by using custom built in-house IRT system and commercial turnkey system. The analysis and experimental results showed good correlation between thermal diffusivity value and anomalies within the disk. It was demonstrated that the step-heating transient thermal approach could be effectively applied to obtain the whole field thermal diffusivity value of C/C composites.

  5. Mathematical Simulation of Graphene With Modified c-c Bond Length and Transfer Energy

    Directory of Open Access Journals (Sweden)

    P.A. Alvi

    2011-01-01

    Full Text Available In nanotechnology research, allotropes of carbon like Graphene, Fullerene (Buckyball and Carbon nanotubes are widely used due to their remarkable properties. Electrical and mechanical properties of those allotropes vary with their molecular geometry. This paper is specially based on modeling and simulation of graphene in order to calculate energy band structure in k space with varying the C-C bond length and C-C transfer energy. Significant changes have been observed in the energy band structure of graphene due to variation in C-C bond length and C-C transfer energy. In particular, this paper focuses over the electronic structure of graphene within the frame work of tight binding approximation. It has been reported that conduction and valence states in graphene only meet at two points in k-space and that dispersion around these special points is conical.

  6. Observation of the decay $\\psi(3686)$ $\\rightarrow$ $\\Lambda\\bar\\Sigma^{\\pm}\\pi^{\\mp}+c.c.$

    CERN Document Server

    Ablikim, M; Ai, X C; Albayrak, O; Ambrose, D J; An, F F; An, Q; Bai, J Z; A, R Baldini Ferroli; Ban, Y; Bennett, J V; A, M Bertani; Bian, J M; Boger, E; Bondarenko, O; Boyko, I; Braun, S; Briere, R A; Cai, H; Cai, X; A, O Cakir; A, A Calcaterra; Cao, G F; B, S A Cetin; Chang, J F; Chelkov, G; Chen, G; Chen, H S; Chen, J C; Chen, M L; Chen, S J; Chen, X; Chen, X R; Chen, Y B; Cheng, H P; Chu, X K; Chu, Y P; Cronin-Hennessy, D; Dai, H L; Dai, J P; Dedovich, D; Deng, Z Y; Denig, A; Denysenko, I; Destefanis, M; Ding, W M; Ding, Y; Dong, C; Dong, J; Dong, L Y; Dong, M Y; Du, S X; Fang, J; Fang, S S; Fang, Y; Fava, L; Feng, C Q; Fu, C D; Fu, J L; Fuks, O; Gao, Q; Gao, Y; Geng, C; Goetzen, K; Gong, W X; Gradl, W; Greco, M; Gu, M H; Gu, Y T; Guan, Y H; Guo, A Q; Guo, L B; Guo, T; Guo, Y P; Han, Y L; Harris, F A; He, K L; He, M; He, Z Y; Held, T; Heng, Y K; Hou, Z L; Hu, C; Hu, H M; Hu, J F; Hu, T; Huang, G M; Huang, G S; Huang, J S; Huang, L; Huang, X T; Hussain, T; Ji, C S; Ji, Q; Ji, Q P; Ji, X B; Ji, X L; Jiang, L L; Jiang, X S; Jiao, J B; Jiao, Z; Jin, D P; Jin, S; Jing, F F; Johansson, T; Kalantar-Nayestanaki, N; Kang, X L; Kavatsyuk, M; Kloss, B; Kopf, B; Kornicer, M; Kuehn, W; Kupsc, A; Lai, W; Lange, J S; Lara, M; Larin, P; Leyhe, M; Li, C H; Li, Cheng; Li, Cui; Li, D; Li, D M; Li, F; Li, G; Li, H B; Li, J C; Li, K; Li, Lei; Li, P R; Li, Q J; Li, T; Li, W D; Li, W G; Li, X L; Li, X N; Li, X Q; Li, X R; Li, Z B; Liang, H; Liang, Y F; Liang, Y T; Liao, G R; Lin, D X; Liu, B J; Liu, C L; Liu, C X; Liu, F H; Liu, Fang; Liu, Feng; Liu, H B; Liu, H H; Liu, H M; Liu, J; Liu, J P; Liu, K; Liu, K Y; Liu, P L; Liu, Q; Liu, S B; Liu, X; Liu, Y B; Liu, Z A; Liu, Zhiqiang; Liu, Zhiqing; Loehner, H; Lou, X C; Lu, G R; Lu, H J; Lu, H L; Lu, J G; Lu, X R; Lu, Y; Lu, Y P; Luo, C L; Luo, M X; Luo, T; Luo, X L; Lv, M; Ma, F C; Ma, H L; Ma, Q M; Ma, S; Ma, T; Ma, X Y; Maas, F E; Maggiora, M; Malik, Q A; Mao, Y J; Mao, Z P; Messchendorp, J G; Min, J; Min, T J; Mitchell, R E; Mo, X H; Moeini, H; Morales, C Morales; Moriya, K; Muchnoi, N Yu; Nefedov, Y; Nikolaev, I B; Ning, Z; Nisar, S; Niu, X Y; Olsen, S L; Ouyang, Q; B, S Pacetti; Pelizaeus, M; Peng, H P; Peters, K; Ping, J L; Ping, R G; Poling, R; Prencipe, E; Qi, M; Qian, S; Qiao, C F; Qin, L Q; Qin, X S; Qin, Y; Qin, Z H; Qiu, J F; Rashid, K H; Redmer, C F; Ripka, M; Rong, G; Ruan, X D; Sarantsev, A; Schinning, K; Schumann, S; Shan, W; Shao, M; Shen, C P; Shen, X Y; Sheng, H Y; Shepherd, M R; Song, W M; Song, X Y; Spataro, S; Spruck, B; Sun, G X; Sun, J F; Sun, S S; Sun, Y J; Sun, Y Z; Sun, Z J; Sun, Z T; Tang, C J; Tang, X; Tapan, I; Thorndike, E H; Toth, D; Ullrich, M; B, I Uman; Varner, G S; Wang, B; Wang, D; Wang, D Y; Wang, K; Wang, L L; Wang, L S; Wang, M; Wang, P; Wang, P L; Wang, Q J; Wang, S G; Wang, W; Wang, X F; A, Y D Wang; Wang, Y F; Wang, Y Q; Wang, Z; Wang, Z G; Wang, Z H; Wang, Z Y; Wei, D H; Wei, J B; Weidenkaff, P; Wen, S P; Werner, M; Wiedner, U; Wolke, M; Wu, G G; Wu, L H; Wu, N; Wu, W; Wu, Z; Xia, L G; Xia, Y; Xiao, D; Xiao, Z J; Xie, Y G; Xiu, Q L; Xu, G F; Xu, L; Xu, Q J; Xu, Q N; Xu, X P; Xue, Z; Yan, L; Yan, W B; Yan, W C; Yan, Y H; Yang, H X; Yang, Y; Yang, Y X; Ye, H; Ye, M; Ye, M H; Yu, B X; Yu, C X; Yu, H W; Yu, J S; Yu, S P; Yuan, C Z; Yuan, W L; Yuan, Y; Zafar, A A; A, A Zallo; Zang, S L; Zeng, Y; Zhang, B X; Zhang, B Y; Zhang, C; Zhang, C B; Zhang, C C; Zhang, D H; Zhang, H H; Zhang, H Y; Zhang, J J; Zhang, J L; Zhang, J Q; Zhang, J W; Zhang, J Y; Zhang, J Z; Zhang, S H; Zhang, X J; Zhang, X Y; Zhang, Y; Zhang, Y H; Zhang, Z H; Zhang, Z P; Zhang, Z Y; Zhao, G; Zhao, J W; Zhao, Lei; Zhao, Ling; Zhao, M G; Zhao, Q; Zhao, Q W; Zhao, S J; Zhao, T C; Zhao, X H; Zhao, Y B; Zhao, Z G; Zhemchugov, A; Zheng, B; Zheng, J P; Zheng, Y H; Zhong, B; Zhou, L; Zhou, Li; Zhou, X; Zhou, X K; Zhou, X R; Zhou, X Y; Zhu, K; Zhu, K J; Zhu, X L; Zhu, Y C; Zhu, Y S; Zhu, Z A; Zhuang, J; Zou, B S; Zou, J H

    2013-01-01

    Using a sample of $1.06\\times10^{8}$ $\\psi(3686)$ events collected with the BESIII detector, we present the first observation of the decays of $\\psi(3686)$ $\\rightarrow$ $\\Lambda\\bar\\Sigma^{+}\\pi^{-}+c.c.$ and $\\psi(3686)$ $\\rightarrow$ $\\Lambda\\bar\\Sigma^{-}\\pi^{+}+c.c.$. The branching fractions are measured to be $\\mathcal{B}(\\psi(3686) \\rightarrow \\Lambda\\bar\\Sigma^{+}\\pi^{-} + c.c.)=(1.40\\pm 0.03 \\pm 0.13)\\times10^{-4}$ and $\\mathcal{B}(\\psi(3686) \\rightarrow \\Lambda\\bar\\Sigma^{-}\\pi^{+}+c.c.)=(1.54\\pm 0.04 \\pm 0.13)\\times10^{-4}$, where the first errors are statistical and the second ones systematic.

  7. V1R promoters are well conserved and exhibit common putative regulatory motifs

    Directory of Open Access Journals (Sweden)

    Lane Robert P

    2007-07-01

    Full Text Available Abstract Background The mouse vomeronasal organ (VNO processes chemosensory information, including pheromone signals that influence reproductive behaviors. The sensory neurons of the VNO express two types of chemosensory receptors, V1R and V2R. There are ~165 V1R genes in the mouse genome that have been classified into ~12 divergent subfamilies. Each sensory neuron of the apical compartment of the VNO transcribes only one of the repertoire of V1R genes. A model for mutually exclusive V1R transcription in these cells has been proposed in which each V1R gene might compete stochastically for a single transcriptional complex. This model predicts that the large repertoire of divergent V1R genes in the mouse genome contains common regulatory elements. In this study, we have characterized V1R promoter regions by comparative genomics and by mapping transcription start sites. Results We find that transcription is initiated from ~1 kb promoter regions that are well conserved within V1R subfamilies. While cross-subfamily homology is not evident by traditional methods, we developed a heuristic motif-searching tool, LogoAlign, and applied this tool to identify motifs shared within the promoters of all V1R genes. Our motif-searching tool exhibits rapid convergence to a relatively small number of non-redundant solutions (97% convergence. We also find that the best motifs contain significantly more information than those identified in controls, and that these motifs are more likely to be found in the immediate vicinity of transcription start sites than elsewhere in gene blocks. The best motifs occur near transcription start sites of ~90% of all V1R genes and across all of the divergent subfamilies. Therefore, these motifs are candidate binding sites for transcription factors involved in V1R co-regulation. Conclusion Our analyses show that V1R subfamilies have broad and well conserved promoter regions from which transcription is initiated. Results from a new

  8. Type 2 diabetes mellitus: phylogenetic motifs for predicting protein functional sites

    Indian Academy of Sciences (India)

    Ashok Sharma; Tanuja Rastogi; Meenakshi Bhartiya; A K Shasany; S P S Khanuja

    2007-08-01

    Diabetes mellitus, commonly referred to as diabetes, is a medical condition associated with abnormally high levels of glucose (or sugar) in the blood. Keeping this view, we demonstrate the phylogenetic motifs (PMs) identification in type 2 diabetes mellitus very likely corresponding to protein functional sites. In this article, we have identified PMs for all the candidate genes for type 2 diabetes mellitus. Glycine 310 remains conserved for glucokinase and potassium channel KCNJ11. Isoleucine 137 was conserved for insulin receptor and regulatory subunit of a phosphorylating enzyme. Whereas residues valine, leucine, methionine were highly conserved for insulin receptor. Occurrence of proline was very high for calpain 10 gene and glucose transporter

  9. OSCAR is a collagen receptor that costimulates osteoclastogenesis in DAP12-deficient humans and mice

    DEFF Research Database (Denmark)

    Barrow, Alexander David; Raynal, Nicolas; Levin Andersen, Thomas;

    2011-01-01

    Osteoclasts are terminally differentiated leukocytes that erode the mineralized bone matrix. Osteoclastogenesis requires costimulatory receptor signaling through adaptors containing immunoreceptor tyrosine-based activation motifs (ITAMs), such as Fc receptor common γ (FcRγ) and DNAX-activating pr...

  10. Using SCOPE to identify potential regulatory motifs in coregulated genes.

    Science.gov (United States)

    Martyanov, Viktor; Gross, Robert H

    2011-05-31

    SCOPE is an ensemble motif finder that uses three component algorithms in parallel to identify potential regulatory motifs by over-representation and motif position preference. Each component algorithm is optimized to find a different kind of motif. By taking the best of these three approaches, SCOPE performs better than any single algorithm, even in the presence of noisy data. In this article, we utilize a web version of SCOPE to examine genes that are involved in telomere maintenance. SCOPE has been incorporated into at least two other motif finding programs and has been used in other studies. The three algorithms that comprise SCOPE are BEAM, which finds non-degenerate motifs (ACCGGT), PRISM, which finds degenerate motifs (ASCGWT), and SPACER, which finds longer bipartite motifs (ACCnnnnnnnnGGT). These three algorithms have been optimized to find their corresponding type of motif. Together, they allow SCOPE to perform extremely well. Once a gene set has been analyzed and candidate motifs identified, SCOPE can look for other genes that contain the motif which, when added to the original set, will improve the motif score. This can occur through over-representation or motif position preference. Working with partial gene sets that have biologically verified transcription factor binding sites, SCOPE was able to identify most of the rest of the genes also regulated by the given transcription factor. Output from SCOPE shows candidate motifs, their significance, and other information both as a table and as a graphical motif map. FAQs and video tutorials are available at the SCOPE web site which also includes a "Sample Search" button that allows the user to perform a trial run. Scope has a very friendly user interface that enables novice users to access the algorithm's full power without having to become an expert in the bioinformatics of motif finding. As input, SCOPE can take a list of genes, or FASTA sequences. These can be entered in browser text fields, or read from

  11. Indole-3-carbinol and 3’, 3’-diindolylmethane modulate androgen effect up-regulation on C-C chemokine ligand 2 and monocyte attraction to prostate cancer cells

    Science.gov (United States)

    Inflammation has a role in prostate tumorigenesis. Recruitment of inflammatory monocytes to the tumor site is mediated by C-C chemokine ligand 2 (CCL2) through binding to its receptor CCR2. We hypothesized that androgen could modulate CCL2 expression in hormone-responsive prostate cancer cells, and ...

  12. Receptor-like Kinase CrRLK1-L Subfamily: Novel Motifs in Extracellular Domain and Biological Functions in Plants%植物类受体激酶CrRLK1-L亚家族及其生物学功能

    Institute of Scientific and Technical Information of China (English)

    韩永峰; 杨倩; 张胜伟; 孙大业; 孙颖

    2011-01-01

    CrRLKl-L receptor-like kinases (RLKs) possess novel motifs with unknown functions in the extracellular domain and the typical Ser/Thr kinase domain in the intracellular region. CrRLKl-L subfamily spread broadly in angiosperm, however, no homologs of CrRLKl-L proteins exist in animals and microorganisms. CrRLKl-L RLKs express extensively in most of tissues, and mainly involve in signal exchanging between male and female gametophytes, the sensing of cell-wall-integrality and cell elongation control of the vegetative organs, and also in the response of cell to diverse biotic stress, etc. CrRLKl-L RLKs commonly localize on plasm-membrane, and their kinase activity is essential for their biological functions. Therefore, CrRLKl-L RLKs can function as cell surface sensor for extracellular signal and initiate a signal transduction that largely independent of the known phytohormone signaling pathways. Detailed study of CrRLKl-L RLKs gene functions will be helpful for our understanding the molecular mechanisms in the special biological processes in plant, especially in sexual reproduction in that optimal utilization will benefit the agriculture production in future.%植物CrRLK1-L亚家族类受体激酶的胞外域具有新颖结构基序,但功能大都未知.该家族成员广泛存在于被子植物中,但在动物和微生物中不存在其同源物.CrRLK1-L家族成员相对较少,但组织表达非常广泛.它们定位于细胞质膜上,并且部分成员的定位还具有极性,这与其参与雌雄配子体的识别和受精作用密切相关.该家族成员普遍具有激酶活性,该活性对其功能的发挥至关重要.目前仅报道在拟南芥中参与助细胞与花粉的识别和调控营养组织的细胞伸长,但参与这些生物学过程的作用机制似乎独立于已知的信号通路之外,可能有自身独特的信号传导机制.所以对这一类具特有结构基序的类受体激酶基因的功能研究,将有助于解析植物特有生物

  13. Anticipated synchronization in neuronal network motifs

    Science.gov (United States)

    Matias, F. S.; Gollo, L. L.; Carelli, P. V.; Copelli, M.; Mirasso, C. R.

    2013-01-01

    Two identical dynamical systems coupled unidirectionally (in a so called master-slave configuration) exhibit anticipated synchronization (AS) if the one which receives the coupling (the slave) also receives a negative delayed self-feedback. In oscillatory neuronal systems AS is characterized by a phase-locking with negative time delay τ between the spikes of the master and of the slave (slave fires before the master), while in the usual delayed synchronization (DS) regime τ is positive (slave fires after the master). A 3-neuron motif in which the slave self-feedback is replaced by a feedback loop mediated by an interneuron can exhibits both AS and DS regimes. Here we show that AS is robust in the presence of noise in a 3 Hodgkin-Huxley type neuronal motif. We also show that AS is stable for large values of τ in a chain of connected slaves-interneurons.

  14. Locomotif - a graphical programming system for RNA motif search

    OpenAIRE

    Reeder, Janina

    2006-01-01

    In this thesis, I am presenting the results of my work in designing, implementing and installing a software environment for RNA motif searches: Locomotif. It includes a visual editor for motif definition, translation of the motif structure to XML code and client-server interactions, and further, translation of the XML code to ADP and compilation to C.

  15. MENGUNGKAP SEJARAH DAN MOTIF BATIK SEMARANGAN

    Directory of Open Access Journals (Sweden)

    Dewi Yuliati

    2011-10-01

    Full Text Available Batik Semarang was born in line with the needs of the people of Hyderabad of the material with a new motif or style tailored to the taste, intention, and creativity of the craftsmen. Batik is a combination of several countries influence developing in Indonesian culture. Based on its shape, Batik designs can be divided into two major groups, namely geometric and non-Geometric. The development of Semarangan batik was due to the fact that certain motif of batik can only be worn by certain people, not for all group of people. Batik semarangan craftments are found in coastal regions. It displays the design composing of ornaments plucked from marine environment. Indonesian Batik develops not only to display a blending of court Batik designs with the coastal Batik technique, but also to incorporate other ornaments which come from many various ethnic groups in Indonesia.   Key words: batik, history, ornaments, marine environment, designs   Batik Semarang lahirkan sejalan dengan kebutuhan dari orang-orang dari Hyderabad akan bahan dengan motif atau gaya baru yang berdasarkan pada rasa, niat, dan kreatifitas dari pembuatnya. Batik merupakan perpaduan dari pengaruh beberapa negara yang berkembang dalam budaya Indonesia. Ditinjau dari desainnya, desain batik dapat dibagi menjadi dua kelompok utama, yakni geometrik dan nongeometrik. Pengembangan yang dilakukan terhadap batik semarangan disebabkan adanya beberapa motif batik yang hanya digunakan oleh kalangan tertentu, dan tidak boleh untuk kalangan umum. Pengrajin batik Semarangan berkembang di kawasan pesisir. Ia menampilkan desain yang terdiri atas berbagai ornamen yang menunjukkan ciri khas kemaritiman. Batik ini dikembangakan tidak hanya menampilkan desain batik khas pesisiran, tetapi juga memasukkan berbagai ornament dari beragam kelompok etnis di Indonesia.   Kata kunci: batik, sejarah, ragam hias, lingkungan pesisir, desain  

  16. Multilayer motif analysis of brain networks

    OpenAIRE

    Battiston, Federico; Nicosia, Vincenzo; Chavez, Mario; Latora, Vito

    2016-01-01

    In the last decade network science has shed new light on the anatomical connectivity and on correlations in the activity of different areas of the human brain. The study of brain networks has made possible in fact to detect the central areas of a neural system, and to identify its building blocks by looking at overabundant small subgraphs, known as motifs. However, network analysis of the brain has so far mainly focused on structural and functional networks as separate entities. The recently ...

  17. Multilayer motif analysis of brain networks

    CERN Document Server

    Battiston, Federico; Chavez, Mario; Latora, Vito

    2016-01-01

    In the last decade network science has shed new light on the anatomical connectivity and on correlations in the activity of different areas of the human brain. The study of brain networks has made possible in fact to detect the central areas of a neural system, and to identify its building blocks by looking at overabundant small subgraphs, known as motifs. However, network analysis of the brain has so far mainly focused on structural and functional networks as separate entities. The recently developed mathematical framework of multi-layer networks allows to perform a multiplex analysis of the human brain where the structural and functional layers are considered at the same time. In this work we describe how to classify subgraphs in multiplex networks, and we extend motif analysis to networks with many layers. We then extract multi-layer motifs in brain networks of healthy subjects by considering networks with two layers, respectively obtained from diffusion and functional magnetic resonance imaging. Results i...

  18. Discovering sequence motifs with arbitrary insertions and deletions.

    Directory of Open Access Journals (Sweden)

    Martin C Frith

    2008-04-01

    Full Text Available BIOLOGY IS ENCODED IN MOLECULAR SEQUENCES: deciphering this encoding remains a grand scientific challenge. Functional regions of DNA, RNA, and protein sequences often exhibit characteristic but subtle motifs; thus, computational discovery of motifs in sequences is a fundamental and much-studied problem. However, most current algorithms do not allow for insertions or deletions (indels within motifs, and the few that do have other limitations. We present a method, GLAM2 (Gapped Local Alignment of Motifs, for discovering motifs allowing indels in a fully general manner, and a companion method GLAM2SCAN for searching sequence databases using such motifs. glam2 is a generalization of the gapless Gibbs sampling algorithm. It re-discovers variable-width protein motifs from the PROSITE database significantly more accurately than the alternative methods PRATT and SAM-T2K. Furthermore, it usefully refines protein motifs from the ELM database: in some cases, the refined motifs make orders of magnitude fewer overpredictions than the original ELM regular expressions. GLAM2 performs respectably on the BAliBASE multiple alignment benchmark, and may be superior to leading multiple alignment methods for "motif-like" alignments with N- and C-terminal extensions. Finally, we demonstrate the use of GLAM2 to discover protein kinase substrate motifs and a gapped DNA motif for the LIM-only transcriptional regulatory complex: using GLAM2SCAN, we identify promising targets for the latter. GLAM2 is especially promising for short protein motifs, and it should improve our ability to identify the protein cleavage sites, interaction sites, post-translational modification attachment sites, etc., that underlie much of biology. It may be equally useful for arbitrarily gapped motifs in DNA and RNA, although fewer examples of such motifs are known at present. GLAM2 is public domain software, available for download at http://bioinformatics.org.au/glam2.

  19. Large-scale discovery of promoter motifs in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Thomas A Down

    2007-01-01

    Full Text Available A key step in understanding gene regulation is to identify the repertoire of transcription factor binding motifs (TFBMs that form the building blocks of promoters and other regulatory elements. Identifying these experimentally is very laborious, and the number of TFBMs discovered remains relatively small, especially when compared with the hundreds of transcription factor genes predicted in metazoan genomes. We have used a recently developed statistical motif discovery approach, NestedMICA, to detect candidate TFBMs from a large set of Drosophila melanogaster promoter regions. Of the 120 motifs inferred in our initial analysis, 25 were statistically significant matches to previously reported motifs, while 87 appeared to be novel. Analysis of sequence conservation and motif positioning suggested that the great majority of these discovered motifs are predictive of functional elements in the genome. Many motifs showed associations with specific patterns of gene expression in the D. melanogaster embryo, and we were able to obtain confident annotation of expression patterns for 25 of our motifs, including eight of the novel motifs. The motifs are available through Tiffin, a new database of DNA sequence motifs. We have discovered many new motifs that are overrepresented in D. melanogaster promoter regions, and offer several independent lines of evidence that these are novel TFBMs. Our motif dictionary provides a solid foundation for further investigation of regulatory elements in Drosophila, and demonstrates techniques that should be applicable in other species. We suggest that further improvements in computational motif discovery should narrow the gap between the set of known motifs and the total number of transcription factors in metazoan genomes.

  20. Irradiation effects on C/C composite materials for high temperature nuclear applications

    International Nuclear Information System (INIS)

    Excellent characteristics such as high strength and high thermal shock resistance of C/C composite materials have led us to try to apply them to the high temperature components in nuclear facilities. Such components include the armour tile of the first wall and divertor of fusion reactor and the elements of control rod for the use in HTGR. One of the most important aspects to be clarified about C/C composites for nuclear applications is the effect of neutron irradiation on their properties. At the Japan Atomic Energy Research Institute (JAERI), research on the irradiation effects on various properties of C/C composite materials has been carried out using fission reactors (JRR-3, JMTR), accelerators (TANDEM, TIARA) and the Fusion Neutronics Source (FNS). Additionally, strength tests of some neutron-irradiated elements for the control rod were carried out to investigate the feasibility of C/C composites. The paper summarises the R and D activities on the irradiation effects on C/C composites. (authors)

  1. ET-Motif: Solving the Exact (l, d)-Planted Motif Problem Using Error Tree Structure.

    Science.gov (United States)

    Al-Okaily, Anas; Huang, Chun-Hsi

    2016-07-01

    Motif finding is an important and a challenging problem in many biological applications such as discovering promoters, enhancers, locus control regions, transcription factors, and more. The (l, d)-planted motif search, PMS, is one of several variations of the problem. In this problem, there are n given sequences over alphabets of size [Formula: see text], each of length m, and two given integers l and d. The problem is to find a motif m of length l, where in each sequence there is at least an l-mer at a Hamming distance of [Formula: see text] of m. In this article, we propose ET-Motif, an algorithm that can solve the PMS problem in [Formula: see text] time and [Formula: see text] space. The time bound can be further reduced by a factor of m with [Formula: see text] space. In case the suffix tree that is built for the input sequences is balanced, the problem can be solved in [Formula: see text] time and [Formula: see text] space. Similarly, the time bound can be reduced by a factor of m using [Formula: see text] space. Moreover, the variations of the problem, namely the edit distance PMS and edited PMS (Quorum), can be solved using ET-Motif with simple modifications but upper bands of space and time. For edit distance PMS, the time and space bounds will be increased by [Formula: see text], while for edited PMS the increase will be of [Formula: see text] in the time bound. PMID:27152692

  2. Dynamics of network motifs in genetic regulatory networks

    Institute of Scientific and Technical Information of China (English)

    Li Ying; Liu Zeng-Rong; Zhang Jian-Bao

    2007-01-01

    Network motifs hold a very important status in genetic regulatory networks. This paper aims to analyse the dynamical property of the network motifs in genetic regulatory networks. The main result we obtained is that the dynamical property of a single motif is very simple with only an asymptotically stable equilibrium point, but the combination of several motifs can make more complicated dynamical properties emerge such as limit cycles. The above-mentioned result shows that network motif is a stable substructure in genetic regulatory networks while their combinations make the genetic regulatory network more complicated.

  3. A dinucleotide motif in oligonucleotides shows potent immunomodulatory activity and overrides species-specific recognition observed with CpG motif

    OpenAIRE

    Kandimalla, Ekambar R; Bhagat, Lakshmi; Zhu, Fu-Gang; Yu, Dong; Cong, Yan-Ping; Wang, Daqing; Tang, Jimmy X.; Tang, Jin-Yan; Knetter, Cathrine F.; Lien, Egil; Agrawal, Sudhir

    2003-01-01

    Bacterial and synthetic DNAs containing CpG dinucleotides in specific sequence contexts activate the vertebrate immune system through Toll-like receptor 9 (TLR9). In the present study, we used a synthetic nucleoside with a bicyclic heterobase [1-(2′-deoxy-β-d-ribofuranosyl)-2-oxo-7-deaza-8-methyl-purine; R] to replace the C in CpG, resulting in an RpG dinucleotide. The RpG dinucleotide was incorporated in mouse- and human-specific motifs in oligodeoxynucleotides (oligos) and 3′-3-linked oligo...

  4. Iterative reactions of transient boronic acids enable sequential C-C bond formation

    Science.gov (United States)

    Battilocchio, Claudio; Feist, Florian; Hafner, Andreas; Simon, Meike; Tran, Duc N.; Allwood, Daniel M.; Blakemore, David C.; Ley, Steven V.

    2016-04-01

    The ability to form multiple carbon-carbon bonds in a controlled sequence and thus rapidly build molecular complexity in an iterative fashion is an important goal in modern chemical synthesis. In recent times, transition-metal-catalysed coupling reactions have dominated in the development of C-C bond forming processes. A desire to reduce the reliance on precious metals and a need to obtain products with very low levels of metal impurities has brought a renewed focus on metal-free coupling processes. Here, we report the in situ preparation of reactive allylic and benzylic boronic acids, obtained by reacting flow-generated diazo compounds with boronic acids, and their application in controlled iterative C-C bond forming reactions is described. Thus far we have shown the formation of up to three C-C bonds in a sequence including the final trapping of a reactive boronic acid species with an aldehyde to generate a range of new chemical structures.

  5. Nanowires of silicon carbide and 3D SiC/C nanocomposites with inverse opal structure

    International Nuclear Information System (INIS)

    Synthesis, morphology, structural and optical characteristics of SiC NWs and SiC/C nanocomposites with an inverse opal lattice have been investigated. The samples were prepared by carbothermal reduction of silica (SiC NWs) and by thermo-chemical treatment of opal matrices (SiC/C) filled with carbon compounds which was followed by silicon dioxide dissolution. It was shown that the nucleation of SiC NWs occurs at the surface of carbon fibers felt. It was observed three preferred growth direction of the NWs: [111], [110] and [112]. HRTEM studies revealed the mechanism of the wires growth direction change. SiC/C- HRTEM revealed in the structure of the composites, except for silicon carbide, graphite and amorphous carbon, spherical carbon particles containing concentric graphite shells (onion-like particles).

  6. The EH1 motif in metazoan transcription factors

    Directory of Open Access Journals (Sweden)

    Copley Richard R

    2005-11-01

    Full Text Available Abstract Background The Engrailed Homology 1 (EH1 motif is a small region, believed to have evolved convergently in homeobox and forkhead containing proteins, that interacts with the Drosophila protein groucho (C. elegans unc-37, Human Transducin-like Enhancers of Split. The small size of the motif makes its reliable identification by computational means difficult. I have systematically searched the predicted proteomes of Drosophila, C. elegans and human for further instances of the motif. Results Using motif identification methods and database searching techniques, I delimit which homeobox and forkhead domain containing proteins also have likely EH1 motifs. I show that despite low database search scores, there is a significant association of the motif with transcription factor function. I further show that likely EH1 motifs are found in combination with T-Box, Zinc Finger and Doublesex domains as well as discussing other plausible candidate associations. I identify strong candidate EH1 motifs in basal metazoan phyla. Conclusion Candidate EH1 motifs exist in combination with a variety of transcription factor domains, suggesting that these proteins have repressor functions. The distribution of the EH1 motif is suggestive of convergent evolution, although in many cases, the motif has been conserved throughout bilaterian orthologs. Groucho mediated repression was established prior to the evolution of bilateria.

  7. CLIMP: Clustering Motifs via Maximal Cliques with Parallel Computing Design.

    Science.gov (United States)

    Zhang, Shaoqiang; Chen, Yong

    2016-01-01

    A set of conserved binding sites recognized by a transcription factor is called a motif, which can be found by many applications of comparative genomics for identifying over-represented segments. Moreover, when numerous putative motifs are predicted from a collection of genome-wide data, their similarity data can be represented as a large graph, where these motifs are connected to one another. However, an efficient clustering algorithm is desired for clustering the motifs that belong to the same groups and separating the motifs that belong to different groups, or even deleting an amount of spurious ones. In this work, a new motif clustering algorithm, CLIMP, is proposed by using maximal cliques and sped up by parallelizing its program. When a synthetic motif dataset from the database JASPAR, a set of putative motifs from a phylogenetic foot-printing dataset, and a set of putative motifs from a ChIP dataset are used to compare the performances of CLIMP and two other high-performance algorithms, the results demonstrate that CLIMP mostly outperforms the two algorithms on the three datasets for motif clustering, so that it can be a useful complement of the clustering procedures in some genome-wide motif prediction pipelines. CLIMP is available at http://sqzhang.cn/climp.html. PMID:27487245

  8. CLIMP: Clustering Motifs via Maximal Cliques with Parallel Computing Design.

    Science.gov (United States)

    Zhang, Shaoqiang; Chen, Yong

    2016-01-01

    A set of conserved binding sites recognized by a transcription factor is called a motif, which can be found by many applications of comparative genomics for identifying over-represented segments. Moreover, when numerous putative motifs are predicted from a collection of genome-wide data, their similarity data can be represented as a large graph, where these motifs are connected to one another. However, an efficient clustering algorithm is desired for clustering the motifs that belong to the same groups and separating the motifs that belong to different groups, or even deleting an amount of spurious ones. In this work, a new motif clustering algorithm, CLIMP, is proposed by using maximal cliques and sped up by parallelizing its program. When a synthetic motif dataset from the database JASPAR, a set of putative motifs from a phylogenetic foot-printing dataset, and a set of putative motifs from a ChIP dataset are used to compare the performances of CLIMP and two other high-performance algorithms, the results demonstrate that CLIMP mostly outperforms the two algorithms on the three datasets for motif clustering, so that it can be a useful complement of the clustering procedures in some genome-wide motif prediction pipelines. CLIMP is available at http://sqzhang.cn/climp.html.

  9. No tradeoff between versatility and robustness in gene circuit motifs

    Science.gov (United States)

    Payne, Joshua L.

    2016-05-01

    Circuit motifs are small directed subgraphs that appear in real-world networks significantly more often than in randomized networks. In the Boolean model of gene circuits, most motifs are realized by multiple circuit genotypes. Each of a motif's constituent circuit genotypes may have one or more functions, which are embodied in the expression patterns the circuit forms in response to specific initial conditions. Recent enumeration of a space of nearly 17 million three-gene circuit genotypes revealed that all circuit motifs have more than one function, with the number of functions per motif ranging from 12 to nearly 30,000. This indicates that some motifs are more functionally versatile than others. However, the individual circuit genotypes that constitute each motif are less robust to mutation if they have many functions, hinting that functionally versatile motifs may be less robust to mutation than motifs with few functions. Here, I explore the relationship between versatility and robustness in circuit motifs, demonstrating that functionally versatile motifs are robust to mutation despite the inherent tradeoff between versatility and robustness at the level of an individual circuit genotype.

  10. Chemokine receptor CCR8 is required for lipopolysaccharide-triggered cytokine production in mouse peritoneal macrophages.

    Directory of Open Access Journals (Sweden)

    Tomoyuki Oshio

    Full Text Available Chemokine (C-C motif receptor 8 (CCR8, the chemokine receptor for chemokine (C-C motif ligand 1 (CCL1, is expressed in T-helper type-2 lymphocytes and peritoneal macrophages (PMφ and is involved in various pathological conditions, including peritoneal adhesions. However, the role of CCR8 in inflammatory responses is not fully elucidated. To investigate the function of CCR8 in macrophages, we compared cytokine secretion from mouse PMφ or bone marrow-derived macrophages (BMMφ stimulated with various Toll-like receptor (TLR ligands in CCR8 deficient (CCR8-/- and wild-type (WT mice. We found that CCR8-/- PMφ demonstrated attenuated secretion of tumor necrosis factor (TNF-α, interleukin (IL-6, and IL-10 when stimulated with lipopolysaccharide (LPS. In particular, LPS-induced IL-10 production absolutely required CCR8. CCR8-dependent cytokine secretion was characteristic of PMφ but not BMMφ. To further investigate this result, we selected the small molecule compound R243 from a library of compounds with CCR8-antagonistic effects on CCL1-induced Ca2+ flux and CCL1-driven PMφ aggregation. Similar to CCR8-/- PMφ, R243 attenuated secretion of TNF-α, IL-6, and most strikingly IL-10 from WT PMφ, but not BMMφ. CCR8-/- PMφ and R243-treated WT PMφ both showed suppressed c-jun N-terminal kinase activity and nuclear factor-κB signaling after LPS treatment when compared with WT PMφ. A c-Jun signaling pathway inhibitor also produced an inhibitory effect on LPS-induced cytokine secretion that was similar to that of CCR8 deficiency or R243 treatment. As seen in CCR8-/- mice, administration of R243 attenuated peritoneal adhesions in vivo. R243 also prevented hapten-induced colitis. These results are indicative of cross talk between signaling pathways downstream of CCR8 and TLR-4 that induces cytokine production by PMφ. Through use of CCR8-/- mice and the new CCR8 inhibitor, R243, we identified a novel macrophage innate immune response pathway that

  11. AISMOTIF-An Artificial Immune System for DNA Motif Discovery

    Directory of Open Access Journals (Sweden)

    Seeja K R

    2011-03-01

    Full Text Available Discovery of transcription factor binding sites is a much explored and still exploring area of research in functional genomics. Many computational tools have been developed for finding motifs and each of them has their own advantages as well as disadvantages. Most of these algorithms need prior knowledge about the data to construct background models. However there is not a single technique that can be considered as best for finding regulatory motifs. This paper proposes an artificial immune system based algorithm for finding the transcription factor binding sites or motifs and two new weighted scores for motif evaluation. The algorithm is enumerative, but sufficient pruning of the pattern search space has been incorporated using immune system concepts. The performance of AISMOTIF has been evaluated by comparing it with eight state of art composite motif discovery algorithms and found that AISMOTIF predicts known motifs as well as new motifs from the benchmark dataset without any prior knowledge about the data.

  12. AISMOTIF-An Artificial Immune System for DNA Motif Discovery

    CERN Document Server

    Seeja, K R

    2011-01-01

    Discovery of transcription factor binding sites is a much explored and still exploring area of research in functional genomics. Many computational tools have been developed for finding motifs and each of them has their own advantages as well as disadvantages. Most of these algorithms need prior knowledge about the data to construct background models. However there is not a single technique that can be considered as best for finding regulatory motifs. This paper proposes an artificial immune system based algorithm for finding the transcription factor binding sites or motifs and two new weighted scores for motif evaluation. The algorithm is enumerative, but sufficient pruning of the pattern search space has been incorporated using immune system concepts. The performance of AISMOTIF has been evaluated by comparing it with eight state of art composite motif discovery algorithms and found that AISMOTIF predicts known motifs as well as new motifs from the benchmark dataset without any prior knowledge about the data...

  13. Characterization of C/C composites porosity for the fusion; Caracterisation de la porosite de composites C/C d'interet pour la fusion

    Energy Technology Data Exchange (ETDEWEB)

    Martin, C.; Ballet, A.C.; Pardanaud, C.; Roubin, P. [Universite de Provence, Centre St-Jerome, Laboratoire PIIM, 13 - Marseille (France); Beurroies, I.; Richou, M. [Universite de Provence, Centre St-Jerome, Laboratoire Madirel, 13 - Marseille (France); Brosset, C.; Pegourie, B. [Association EURATOM-CEA sur la Fusion Controlee, CE Cadarache, 13 - St-Paul-lez-Durance (France)

    2008-07-01

    In tokamaks, the composites C/C are used as components facing the plasma because of their excellent thermo-mechanical properties. In Tore Supra tokamak, analysis of particles of graphite erosion showed a big deuterium retention by the machine wall. This fuel retention will lead in ITER to a non acceptable level of tritium. As the diffusion in materials is bound to the porosity, the authors realized a study of two composites porosity: N11 and NB31. Different analysis methods have been performed and the temperature or grain size dependence studied. (A.L.B.)

  14. Chaotic motif sampler: detecting motifs from biological sequences by using chaotic neurodynamics

    Science.gov (United States)

    Matsuura, Takafumi; Ikeguchi, Tohru

    Identification of a region in biological sequences, motif extraction problem (MEP) is solved in bioinformatics. However, the MEP is an NP-hard problem. Therefore, it is almost impossible to obtain an optimal solution within a reasonable time frame. To find near optimal solutions for NP-hard combinatorial optimization problems such as traveling salesman problems, quadratic assignment problems, and vehicle routing problems, chaotic search, which is one of the deterministic approaches, has been proposed and exhibits better performance than stochastic approaches. In this paper, we propose a new alignment method that employs chaotic dynamics to solve the MEPs. It is called the Chaotic Motif Sampler. We show that the performance of the Chaotic Motif Sampler is considerably better than that of the conventional methods such as the Gibbs Site Sampler and the Neighborhood Optimization for Multiple Alignment Discovery.

  15. Experimental study on thermophysical properties of C/C composites at high temperature

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wei; YI Fa-jun; HAN Jie-cai; MENG Song-he

    2006-01-01

    The coefficient of thermal expansion, thermal diffusivity and specific heat of C/C composites from room temperature to ultra high temperature were experimentally investigated. Thermal conductivity and thermal stress resistance of the composites were therefore computed based on experimental results. The results show that the composite has a very low thermal expansion coefficient. Thermal diffusivity decreases exponentially with temperature increase. The specific heat increases linearly as the temperature rises, and the variation trend of thermal conductivity is similar to that of thermal diffusivity. The thermal stress coefficient of C/C composite has little change with temperature variation, and thermal stress resistance of the composite at high temperature is stable.

  16. Monitoring and Diagnostics for C/C++ Real-Time Applications

    CERN Document Server

    Fischer, Yves

    Knowledge about the internal state of computational processes is essential for problem diagnostics as well as for constant monitoring and pre-failure recognition. The CMX li- brary provides monitoring capabilities similiar to the Java Management Extensions (JMX) for C and C++ applications. This thesis provides a detailed analysis of the requirements for monitoring and diagnos- tics of the C/C++ processes at CERN. The developed CMX library enables real-time C/C++ processes to expose values with- out harming their normal execution. CMX is portable and can be integrated in different monitoring architectures.

  17. THE INFLUENCE OF SiC COATING PROCESS ON THE PROPERTIES OF C/C COMPOSITES

    OpenAIRE

    MIN HUANG; KE-ZHI LI; HE-JUN LI; QIAN-GANG FU; GUO-DONG SUN

    2007-01-01

    SiC coating for carbon/carbon composites was prepared by pack cementation method. The effects of coating process on the microstructure and the mechanical properties of C/C composites were analyzed by SEM and three-point bending test, respectively. As the infiltrated Si improved the interfaces bonding during the coating process, the flexural strength and flexural modulus of SiC-coated carbon/carbon composites were both increased by about 10% than the naked C/C composites. In addition, the mech...

  18. Assessing the Exceptionality of Coloured Motifs in Networks

    Directory of Open Access Journals (Sweden)

    Lacroix Vincent

    2009-01-01

    Full Text Available Various methods have been recently employed to characterise the structure of biological networks. In particular, the concept of network motif and the related one of coloured motif have proven useful to model the notion of a functional/evolutionary building block. However, algorithms that enumerate all the motifs of a network may produce a very large output, and methods to decide which motifs should be selected for downstream analysis are needed. A widely used method is to assess if the motif is exceptional, that is, over- or under-represented with respect to a null hypothesis. Much effort has been put in the last thirty years to derive -values for the frequencies of topological motifs, that is, fixed subgraphs. They rely either on (compound Poisson and Gaussian approximations for the motif count distribution in Erdös-Rényi random graphs or on simulations in other models. We focus on a different definition of graph motifs that corresponds to coloured motifs. A coloured motif is a connected subgraph with fixed vertex colours but unspecified topology. Our work is the first analytical attempt to assess the exceptionality of coloured motifs in networks without any simulation. We first establish analytical formulae for the mean and the variance of the count of a coloured motif in an Erdös-Rényi random graph model. Using simulations under this model, we further show that a Pólya-Aeppli distribution better approximates the distribution of the motif count compared to Gaussian or Poisson distributions. The Pólya-Aeppli distribution, and more generally the compound Poisson distributions, are indeed well designed to model counts of clumping events. Altogether, these results enable to derive a -value for a coloured motif, without spending time on simulations.

  19. Acidic/IQ Motif Regulator of Calmodulin*

    OpenAIRE

    Putkey, John A.; Waxham, M. Neal; Gaertner, Tara R.; Brewer, Kari J.; Goldsmith, Michael; Kubota, Yoshihisa; Kleerekoper, Quinn K.

    2007-01-01

    The small IQ motif proteins PEP-19 (62 amino acids) and RC3 (78 amino acids) greatly accelerate the rates of Ca2+ binding to sites III and IV in the C-domain of calmodulin (CaM). We show here that PEP-19 decreases the degree of cooperativity of Ca2+ binding to sites III and IV, and we present a model showing that this could increase Ca2+ binding rate constants. Comparative sequence analysis showed that residues 28 to 58 from PEP-19 are conserved in other proteins. This region includes the IQ ...

  20. Development of C/C composite for the core component of the high temperature gas cooled reactor

    Energy Technology Data Exchange (ETDEWEB)

    Park, J. Y.; Kim, W. J.; Ryu, W. S.; Jang, J. H

    2005-01-15

    This report reviewed a state of the art on development of C/C composite for the core components for VHTR and described the followings items. The fabrication methods of C/C composites. Summary on the JAERI report (JAERI-Res 2002-026) on the process screening test for the selection of a proper C/C composite material. Review of the proceedings presented at the GEN-IV VHTR material PMB meeting. A status of the domestic commercial C/C composite. The published property data and the characteristics of the commercial C/C composite.

  1. Mast Cell and Immune Inhibitory Receptors

    Institute of Scientific and Technical Information of China (English)

    Lixin Li; Zhengbin Yao

    2004-01-01

    Modulation by balancing activating and inhibitory receptors constitutes an important mechanism for regulating immune responses. Cells that are activated following ligation of receptors bearing immunoreceptor tyrosine-based activation motifs (ITAMs) can be negatively regulated by other receptors bearing immunoreceptor tyrosine-based inhibition motifs (ITIMs). Human mast cells (MCs) are the major effector cells of type I hypersensitivity and important participants in a number of disease processes. Antigen-mediated aggregation of IgE bound to its high-affinity receptor on MCs initiates a complex series of biochemical events leading to MC activation. With great detailed description and analysis of several inhibitory receptors on human MCs, a central paradigm of negative regulation of human MC activation by these receptors has emerged. Cellular & Molecular Immunology. 2004;1(6):408-415.

  2. Thymoproteasomes produce unique peptide motifs for positive selection of CD8(+) T cells.

    Science.gov (United States)

    Sasaki, Katsuhiro; Takada, Kensuke; Ohte, Yuki; Kondo, Hiroyuki; Sorimachi, Hiroyuki; Tanaka, Keiji; Takahama, Yousuke; Murata, Shigeo

    2015-01-01

    Positive selection in the thymus provides low-affinity T-cell receptor (TCR) engagement to support the development of potentially useful self-major histocompatibility complex class I (MHC-I)-restricted T cells. Optimal positive selection of CD8(+) T cells requires cortical thymic epithelial cells that express β5t-containing thymoproteasomes (tCPs). However, how tCPs govern positive selection is unclear. Here we show that the tCPs produce unique cleavage motifs in digested peptides and in MHC-I-associated peptides. Interestingly, MHC-I-associated peptides carrying these tCP-dependent motifs are enriched with low-affinity TCR ligands that efficiently induce the positive selection of functionally competent CD8(+) T cells in antigen-specific TCR-transgenic models. These results suggest that tCPs contribute to the positive selection of CD8(+) T cells by preferentially producing low-affinity TCR ligand peptides.

  3. Tribological characteristics of C/C-SiC braking composites under dry and wet conditions

    Institute of Scientific and Technical Information of China (English)

    LI Zhuan; XIAO Peng; XIONG Xiang; ZHU Su-hua

    2008-01-01

    C/C-SiC braking composites, based on reinforcement of carbon fibers and rnatrices of carbon and silicon carbide, were fabricated by warm compaction and in situ reaction process. The tribological characteristics of C/C-SiC braking composites under dry and wet conditions were investigated by means of MM-1000 type of friction testing machine. The influence of dry and wet conditions on the tribological characteristics of the C/C-SiC composites was ascertained. Under dry condition, C/C-SiC braking composites show superior tribological characteristics, including high coefficient of friction (0.38), good abrasive resistance (thickness loss is 1.10 μm per cycle) and steady breaking. The main wear mechanism is plastic deformation and abrasion caused by plough. Under wet condition, frictional films form on the worn surface. The coefficient of friction (0.35) could maintain mostly, and the thickness loss (0.70 μm per cycle) reduces to a certain extent. Furthermore, braking curves are steady and adhesion and oxidation are the main wear mechanisms.

  4. Preparation of Biomorphic SiC/C Ceramics from Pine Wood via Supercritical Ethanol Infiltration

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Biomorphic (wood derived) carbide ceramics with an overall composition in the SiC/C was produced by supercritical ethanol infiltration of low viscosity tetraethylorthosilicate/supercritical ethanol into biologically derived carbon templates (CB-templates) and in situ hydrolysis into Si(OH)4-gel, the Si(OH)4-gel was calcined at 1400℃ to promote the polycondensation of Si(OH)4-gel into SiO2-phase and then carbonthermal reduction of the SiO2 with the biocarbon template into highly porous, biomorphic SiC/C ceramics. The phases and morphology conversion mechanism of resulting porous SiC/C ceramics have been investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FT-IR). Experimental results showed that the biomorphic cellular morphology of pinewood charcoal was remained in the porous SiC/C ceramic with high precision that consisted of β-SiC with minority of α-SiC and the remain free carbon existed in amorphous phase.

  5. Revis\\~ao da Constru\\c{c}\\~ao de Modelos Supersim\\'etricos

    CERN Document Server

    Rodríguez, M C

    2001-01-01

    Foi com base neste estudo que fizemos a constru\\c{c}\\~ao da vers\\~ao supersim\\'etrica dos modelos de simetria $SU(3)_{C} \\otimes SU(3)_{L} \\otimes U(1)_{N}$ \\cite{susy331}, apresentado no final da minha tese de doutorado \\cite{mcr1}. Bem como dos estudos fenomenol\\'ogicos subsequente \\cite{mcr}.

  6. Light Induced C-C Coupling of 2-Chlorobenzazoles with Carbamates, Alcohols, and Ethers.

    Science.gov (United States)

    Lipp, Alexander; Lahm, Günther; Opatz, Till

    2016-06-01

    A light induced, transition-metal-free C-C coupling reaction of 2-chlorobenzazoles with aliphatic carbamates, alcohols, and ethers is presented. Inexpensive reagents, namely sodium acetate, benzophenone, water, and acetonitrile, are employed in a simple reaction protocol using a cheap and widely available 25 W energy saving UV-A lamp at ambient temperature. PMID:27128627

  7. RMOD: a tool for regulatory motif detection in signaling network.

    Directory of Open Access Journals (Sweden)

    Jinki Kim

    Full Text Available Regulatory motifs are patterns of activation and inhibition that appear repeatedly in various signaling networks and that show specific regulatory properties. However, the network structures of regulatory motifs are highly diverse and complex, rendering their identification difficult. Here, we present a RMOD, a web-based system for the identification of regulatory motifs and their properties in signaling networks. RMOD finds various network structures of regulatory motifs by compressing the signaling network and detecting the compressed forms of regulatory motifs. To apply it into a large-scale signaling network, it adopts a new subgraph search algorithm using a novel data structure called path-tree, which is a tree structure composed of isomorphic graphs of query regulatory motifs. This algorithm was evaluated using various sizes of signaling networks generated from the integration of various human signaling pathways and it showed that the speed and scalability of this algorithm outperforms those of other algorithms. RMOD includes interactive analysis and auxiliary tools that make it possible to manipulate the whole processes from building signaling network and query regulatory motifs to analyzing regulatory motifs with graphical illustration and summarized descriptions. As a result, RMOD provides an integrated view of the regulatory motifs and mechanism underlying their regulatory motif activities within the signaling network. RMOD is freely accessible online at the following URL: http://pks.kaist.ac.kr/rmod.

  8. A combinatorial optimization approach for diverse motif finding applications

    Directory of Open Access Journals (Sweden)

    Singh Mona

    2006-08-01

    Full Text Available Abstract Background Discovering approximately repeated patterns, or motifs, in biological sequences is an important and widely-studied problem in computational molecular biology. Most frequently, motif finding applications arise when identifying shared regulatory signals within DNA sequences or shared functional and structural elements within protein sequences. Due to the diversity of contexts in which motif finding is applied, several variations of the problem are commonly studied. Results We introduce a versatile combinatorial optimization framework for motif finding that couples graph pruning techniques with a novel integer linear programming formulation. Our approach is flexible and robust enough to model several variants of the motif finding problem, including those incorporating substitution matrices and phylogenetic distances. Additionally, we give an approach for determining statistical significance of uncovered motifs. In testing on numerous DNA and protein datasets, we demonstrate that our approach typically identifies statistically significant motifs corresponding to either known motifs or other motifs of high conservation. Moreover, in most cases, our approach finds provably optimal solutions to the underlying optimization problem. Conclusion Our results demonstrate that a combined graph theoretic and mathematical programming approach can be the basis for effective and powerful techniques for diverse motif finding applications.

  9. Protein functional-group 3D motif and its applications

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Representing and recognizing protein active sites sequence motif (1D motif) and structural motif (3D motif) is an important topic for predicting and designing protein function. Prevalent methods for extracting and searching 3D motif always consider residue as the minimal unit, which have limited sensitivity. Here we present a new spatial representation of protein active sites, called "functional-group 3D motif ", based on the fact that the functional groups inside a residue contribute mostly to its function. Relevant algorithm and computer program are developed, which could be widely used in the function prediction and the study of structural-function relationship of proteins. As a test, we defined a functional-group 3D motif of the catalytic triad and oxyanion hole with the structure of porcine trypsin (PDB code: 1mct) as the template. With our motif-searching program, we successfully found similar sub-structures in trypsins, subtilisins and a/b hydrolases, which show distinct folds but share similar catalytic mechanism. Moreover, this motif can be used to elucidate the structural basis of other proteins with variant catalytic triads by comparing it to those proteins. Finally, we scanned this motif against a non-redundant protein structure database to find its matches, and the results demonstrated the potential application of functional group 3D motif in function prediction. Above all, compared with the other 3D-motif representations on residues, the functional group 3D motif achieves better representation of protein active region, which is more sensitive for protein function prediction.

  10. Anomalous cross-linking by mechlorethamine of DNA duplexes containing C-C mismatch pairs.

    Science.gov (United States)

    Romero, R M; Mitas, M; Haworth, I S

    1999-03-23

    Nitrogen mustards such as mechlorethamine have previously been shown to covalently cross-link DNA through the N7 position of the two guanine bases of a d[GXC].d[GYC] duplex sequence, a so-called 1,3 G-G-cross-link, when X-Y = C-G or T-A. Here, we report the formation of a new mechlorethamine cross-link with the d[GXC].d[GYC] fragment when X-Y is a C-C mismatch pair. Mechlorethamine cross-links this fragment preferentially between the two mismatched cytosine bases, rather than between the guanine bases. The cross-link also forms when one or both of the guanine bases of the d[GCC].d[GCC] fragment are replaced by N7-deazaguanine, and, more generally, forms with any C-C mismatch, regardless of the flanking base pairs. Piperidine cleavage of the cross-link species containing the d[GCC].d[GCC] sequence gives DNA fragments consistent with alkylation at the mismatched cytosine bases. We also provide evidence that the cross-link reaction occurs between the N3 atoms of the two cytosine bases by showing that the formation of the C-C cross-link is pH dependent for both mechlorethamine and chlorambucil. Dimethyl sulfate (DMS) probing of the cross-linked d[GCC].d[GCC] fragment showed that the major groove of the guanine adjacent to the C-C mismatch is still accessible to DMS. In contrast, the known minor groove binder Hoechst 33258 inhibits the cross-link formation with a C-C mismatch pair flanked by A-T base pairs. These results suggest that the C-C mismatch is cross-linked by mechlorethamine in the minor groove. Since C-C pairs may be involved in unusual secondary structures formed by the trinucleotide repeat sequence d[CCG]n, and associated with triplet repeat expansion diseases, mechlorethamine may serve as a useful probe for these structures. PMID:10090751

  11. The network motif architecture of dominance hierarchies.

    Science.gov (United States)

    Shizuka, Daizaburo; McDonald, David B

    2015-04-01

    The widespread existence of dominance hierarchies has been a central puzzle in social evolution, yet we lack a framework for synthesizing the vast empirical data on hierarchy structure in animal groups. We applied network motif analysis to compare the structures of dominance networks from data published over the past 80 years. Overall patterns of dominance relations, including some aspects of non-interactions, were strikingly similar across disparate group types. For example, nearly all groups exhibited high frequencies of transitive triads, whereas cycles were very rare. Moreover, pass-along triads were rare, and double-dominant triads were common in most groups. These patterns did not vary in any systematic way across taxa, study settings (captive or wild) or group size. Two factors significantly affected network motif structure: the proportion of dyads that were observed to interact and the interaction rates of the top-ranked individuals. Thus, study design (i.e. how many interactions were observed) and the behaviour of key individuals in the group could explain much of the variations we see in social hierarchies across animals. Our findings confirm the ubiquity of dominance hierarchies across all animal systems, and demonstrate that network analysis provides new avenues for comparative analyses of social hierarchies. PMID:25762649

  12. The network motif architecture of dominance hierarchies.

    Science.gov (United States)

    Shizuka, Daizaburo; McDonald, David B

    2015-04-01

    The widespread existence of dominance hierarchies has been a central puzzle in social evolution, yet we lack a framework for synthesizing the vast empirical data on hierarchy structure in animal groups. We applied network motif analysis to compare the structures of dominance networks from data published over the past 80 years. Overall patterns of dominance relations, including some aspects of non-interactions, were strikingly similar across disparate group types. For example, nearly all groups exhibited high frequencies of transitive triads, whereas cycles were very rare. Moreover, pass-along triads were rare, and double-dominant triads were common in most groups. These patterns did not vary in any systematic way across taxa, study settings (captive or wild) or group size. Two factors significantly affected network motif structure: the proportion of dyads that were observed to interact and the interaction rates of the top-ranked individuals. Thus, study design (i.e. how many interactions were observed) and the behaviour of key individuals in the group could explain much of the variations we see in social hierarchies across animals. Our findings confirm the ubiquity of dominance hierarchies across all animal systems, and demonstrate that network analysis provides new avenues for comparative analyses of social hierarchies.

  13. VAMP subfamilies identified by specific R-SNARE motifs.

    Science.gov (United States)

    Rossi, Valeria; Picco, Raffaella; Vacca, Marcella; D'Esposito, Maurizio; D'Urso, Michele; Galli, Thierry; Filippini, Francesco

    2004-05-01

    In eukaryotes, interactions among the alpha-helical coiled-coil domains (CCDs) of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) play a pivotal role in mediating the fusion among vesicles and target membranes. Surface residues of such CCDs are major candidates to regulate the specificity of membrane fusion, as they may alter local charge at the interaction layers and surface of the fusion complex, possibly modulating its formation and/or the binding of non-SNARE regulatory factors. Based on alternate patterns in surface residues, we have identified two motifs which group vesicular SNAREs in two novel subfamilies: RG-SNAREs and RD-SNAREs. The RG-SNARE CCD is common to all members of the widely conserved family of long VAMPs or longins and to yeast and non-neuronal VAMPs, possibly mediating "basic" fusion mechanisms; instead, only synaptobrevins from Bilateria share an RD-SNARE CCD, which is likely to mediate interactions to specific, yet unknown, regulatory factors and/or be the landmark of rapid fusion reactions like that mediating the release of neurotransmitters.

  14. A Gibbs sampler for motif detection in phylogenetically close sequences

    Science.gov (United States)

    Siddharthan, Rahul; van Nimwegen, Erik; Siggia, Eric

    2004-03-01

    Genes are regulated by transcription factors that bind to DNA upstream of genes and recognize short conserved ``motifs'' in a random intergenic ``background''. Motif-finders such as the Gibbs sampler compare the probability of these short sequences being represented by ``weight matrices'' to the probability of their arising from the background ``null model'', and explore this space (analogous to a free-energy landscape). But closely related species may show conservation not because of functional sites but simply because they have not had sufficient time to diverge, so conventional methods will fail. We introduce a new Gibbs sampler algorithm that accounts for common ancestry when searching for motifs, while requiring minimal ``prior'' assumptions on the number and types of motifs, assessing the significance of detected motifs by ``tracking'' clusters that stay together. We apply this scheme to motif detection in sporulation-cycle genes in the yeast S. cerevisiae, using recent sequences of other closely-related Saccharomyces species.

  15. MADMX: A Novel Strategy for Maximal Dense Motif Extraction

    CERN Document Server

    Grossi, Roberto; Pisanti, Nadia; Pucci, Geppino; Upfal, Eli; Vandin, Fabio

    2010-01-01

    We develop, analyze and experiment with a new tool, called MADMX, which extracts frequent motifs, possibly including don't care characters, from biological sequences. We introduce density, a simple and flexible measure for bounding the number of don't cares in a motif, defined as the ratio of solid (i.e., different from don't care) characters to the total length of the motif. By extracting only maximal dense motifs, MADMX reduces the output size and improves performance, while enhancing the quality of the discoveries. The efficiency of our approach relies on a newly defined combining operation, dubbed fusion, which allows for the construction of maximal dense motifs in a bottom-up fashion, while avoiding the generation of nonmaximal ones. We provide experimental evidence of the efficiency and the quality of the motifs returned by MADMX

  16. Triadic motifs in the dependence networks of virtual societies

    CERN Document Server

    Xie, Wen-Jie; Jiang, Zhi-Qiang; Zhou, Wei-Xing

    2014-01-01

    In friendship networks, individuals have different numbers of friends, and the closeness or intimacy between an individual and her friends is heterogeneous. Using a statistical filtering method to identify relationships about who depends on whom, we construct dependence networks (which are directed) from weighted friendship networks of avatars in more than two hundred virtual societies of a massively multiplayer online role-playing game (MMORPG). We investigate the evolution of triadic motifs in dependence networks. Several metrics show that the virtual societies evolved through a transient stage in the first two to three weeks and reached a relatively stable stage. We find that the unidirectional loop motif (${\\rm{M}}_9$) is underrepresented and does not appear, open motifs are also underrepresented, while other close motifs are overrepresented. We also find that, for most motifs, the overall level difference of the three avatars in the same motif is significantly lower than average, whereas the sum of ranks...

  17. An Affinity Propagation-Based DNA Motif Discovery Algorithm.

    Science.gov (United States)

    Sun, Chunxiao; Huo, Hongwei; Yu, Qiang; Guo, Haitao; Sun, Zhigang

    2015-01-01

    The planted (l, d) motif search (PMS) is one of the fundamental problems in bioinformatics, which plays an important role in locating transcription factor binding sites (TFBSs) in DNA sequences. Nowadays, identifying weak motifs and reducing the effect of local optimum are still important but challenging tasks for motif discovery. To solve the tasks, we propose a new algorithm, APMotif, which first applies the Affinity Propagation (AP) clustering in DNA sequences to produce informative and good candidate motifs and then employs Expectation Maximization (EM) refinement to obtain the optimal motifs from the candidate motifs. Experimental results both on simulated data sets and real biological data sets show that APMotif usually outperforms four other widely used algorithms in terms of high prediction accuracy.

  18. An Affinity Propagation-Based DNA Motif Discovery Algorithm

    Directory of Open Access Journals (Sweden)

    Chunxiao Sun

    2015-01-01

    Full Text Available The planted (l,d motif search (PMS is one of the fundamental problems in bioinformatics, which plays an important role in locating transcription factor binding sites (TFBSs in DNA sequences. Nowadays, identifying weak motifs and reducing the effect of local optimum are still important but challenging tasks for motif discovery. To solve the tasks, we propose a new algorithm, APMotif, which first applies the Affinity Propagation (AP clustering in DNA sequences to produce informative and good candidate motifs and then employs Expectation Maximization (EM refinement to obtain the optimal motifs from the candidate motifs. Experimental results both on simulated data sets and real biological data sets show that APMotif usually outperforms four other widely used algorithms in terms of high prediction accuracy.

  19. Probabilistic models for semisupervised discriminative motif discovery in DNA sequences.

    Science.gov (United States)

    Kim, Jong Kyoung; Choi, Seungjin

    2011-01-01

    Methods for discriminative motif discovery in DNA sequences identify transcription factor binding sites (TFBSs), searching only for patterns that differentiate two sets (positive and negative sets) of sequences. On one hand, discriminative methods increase the sensitivity and specificity of motif discovery, compared to generative models. On the other hand, generative models can easily exploit unlabeled sequences to better detect functional motifs when labeled training samples are limited. In this paper, we develop a hybrid generative/discriminative model which enables us to make use of unlabeled sequences in the framework of discriminative motif discovery, leading to semisupervised discriminative motif discovery. Numerical experiments on yeast ChIP-chip data for discovering DNA motifs demonstrate that the best performance is obtained between the purely-generative and the purely-discriminative and the semisupervised learning improves the performance when labeled sequences are limited.

  20. SMALL CARBONACEOUS MOLECULES, ETHYLENE OXIDE (c-C2H4O) AND CYCLOPROPENYLIDENE (c-C3H2): SOURCES OF THE UNIDENTIFIED INFRARED BANDS?

    International Nuclear Information System (INIS)

    We suggest that small carbonaceous molecules (SCMs) may be the sources of the unidentified infrared bands (UIRs) and the underlying continuum. We show that the IR spectroscopy of ethylene oxide (EO, c-C2H4O) and cyclopropenylidene (CP, c-C3H2) closely correlates with the major UIR bands at 3.3, 6.2, 7.7, 8.6, and 11.2 μm, the often seen strong bands at 12.7 and 16.4 μm, as well as many minor features. The differences in band locations and shapes between laboratory EO absorption spectra and astrophysical UIR emission spectra are attributed to vibrational anharmonicity, Fermi resonance splitting of nearly degenerate vibration levels, and rotational envelope narrowing due to the low temperatures in space. The excitation mechanism is absorption of UV radiation, primarily Lyα, by SCMs. Photon trapping for this very optically thick transition enhances the absorption by several orders of magnitude. Our abundance analysis for NGC 7027 reveals that the SCM abundance, relative to H2, is ∼3 x 10-9 which compares well to radio measurements of the CP abundance range of ∼10-9-10-7. The origin of the UIR continuum is discussed in terms of emission from vibrationally and rotationally hot SCM UV photodissociation products and UV excitation of rotationally hot SCM species. Radio lines of CP have been seen in numerous astronomical objects, most displaying the UIR bands. EO is also seen, but in fewer objects, none displaying the UIR bands. We theorize that in UIR objects, EO is formed on, and primarily resides on, carbonaceous grains, precluding radio detection of rotational lines. We suggest laboratory experiments, astronomical observations, and theoretical investigations to further evaluate the SCM mechanism for the UIR bands and continuum.

  1. RNA motif search with data-driven element ordering

    OpenAIRE

    Rampasek, L; Jimenez, RM; Luptak, A; Vinar, T; Brejova, B

    2016-01-01

    Background In this paper, we study the problem of RNA motif search in long genomic sequences. This approach uses a combination of sequence and structure constraints to uncover new distant homologs of known functional RNAs. The problem is NP-hard and is traditionally solved by backtracking algorithms. Results We have designed a new algorithm for RNA motif search and implemented a new motif search tool RNArobo. The tool enhances the RNAbob descriptor language, allowing insertions in helices, wh...

  2. Detecting DNA regulatory motifs by incorporating positional trendsin information content

    Energy Technology Data Exchange (ETDEWEB)

    Kechris, Katherina J.; van Zwet, Erik; Bickel, Peter J.; Eisen,Michael B.

    2004-05-04

    On the basis of the observation that conserved positions in transcription factor binding sites are often clustered together, we propose a simple extension to the model-based motif discovery methods. We assign position-specific prior distributions to the frequency parameters of the model, penalizing deviations from a specified conservation profile. Examples with both simulated and real data show that this extension helps discover motifs as the data become noisier or when there is a competing false motif.

  3. Sequence motif discovery with computational genome-wide analysis

    OpenAIRE

    Akashi, Hirofumi; Aoki, Fumio; Toyota, Minoru; Maruyama, Reo; Sasaki, Yasushi; Mita, Hiroaki; Tokura, Hajime; Imai, Kohzoh; Tatsumi, Haruyuki

    2006-01-01

    As a result of the human genome project and advancements in DNA sequencing technology, we can utilize a huge amount of nucleotide sequence data and can search DNA sequence motifs in whole human genome. However, searching motifs with the naked eye is an enormous task and searching throughout the whole genome is absolutely impossible. Therefore, we have developed a computational genome-wide analyzing system for detecting DNA sequence motifs with biological significance. We used a multi-parallel...

  4. A Comparative Study of Bases for Motif Inference

    OpenAIRE

    Pisanti, Nadia; Crochemore, Maxime; Grossi, Roberto; Sagot, Marie-France

    2005-01-01

    International audience Motif inference is at the heart of several time-demanding computational tasks, such as in molecular biology, data mining and identification of structured motifs in sequences, and in data compression, to name a few. In this scenario, a motif is a pattern that appears repeated at least a certain number of times (the quorum), to be of interest. The pattern can be approximated in that some of its characters can be left unspecified (the don't cares). Motif inference is not ...

  5. STEME: a robust, accurate motif finder for large data sets.

    Science.gov (United States)

    Reid, John E; Wernisch, Lorenz

    2014-01-01

    Motif finding is a difficult problem that has been studied for over 20 years. Some older popular motif finders are not suitable for analysis of the large data sets generated by next-generation sequencing. We recently published an efficient approximation (STEME) to the EM algorithm that is at the core of many motif finders such as MEME. This approximation allows the EM algorithm to be applied to large data sets. In this work we describe several efficient extensions to STEME that are based on the MEME algorithm. Together with the original STEME EM approximation, these extensions make STEME a fully-fledged motif finder with similar properties to MEME. We discuss the difficulty of objectively comparing motif finders. We show that STEME performs comparably to existing prominent discriminative motif finders, DREME and Trawler, on 13 sets of transcription factor binding data in mouse ES cells. We demonstrate the ability of STEME to find long degenerate motifs which these discriminative motif finders do not find. As part of our method, we extend an earlier method due to Nagarajan et al. for the efficient calculation of motif E-values. STEME's source code is available under an open source license and STEME is available via a web interface. PMID:24625410

  6. STEME: a robust, accurate motif finder for large data sets.

    Directory of Open Access Journals (Sweden)

    John E Reid

    Full Text Available Motif finding is a difficult problem that has been studied for over 20 years. Some older popular motif finders are not suitable for analysis of the large data sets generated by next-generation sequencing. We recently published an efficient approximation (STEME to the EM algorithm that is at the core of many motif finders such as MEME. This approximation allows the EM algorithm to be applied to large data sets. In this work we describe several efficient extensions to STEME that are based on the MEME algorithm. Together with the original STEME EM approximation, these extensions make STEME a fully-fledged motif finder with similar properties to MEME. We discuss the difficulty of objectively comparing motif finders. We show that STEME performs comparably to existing prominent discriminative motif finders, DREME and Trawler, on 13 sets of transcription factor binding data in mouse ES cells. We demonstrate the ability of STEME to find long degenerate motifs which these discriminative motif finders do not find. As part of our method, we extend an earlier method due to Nagarajan et al. for the efficient calculation of motif E-values. STEME's source code is available under an open source license and STEME is available via a web interface.

  7. Modeling Network Evolution Using Graph Motifs

    CERN Document Server

    Conway, Drew

    2011-01-01

    Network structures are extremely important to the study of political science. Much of the data in its subfields are naturally represented as networks. This includes trade, diplomatic and conflict relationships. The social structure of several organization is also of interest to many researchers, such as the affiliations of legislators or the relationships among terrorist. A key aspect of studying social networks is understanding the evolutionary dynamics and the mechanism by which these structures grow and change over time. While current methods are well suited to describe static features of networks, they are less capable of specifying models of change and simulating network evolution. In the following paper I present a new method for modeling network growth and evolution. This method relies on graph motifs to generate simulated network data with particular structural characteristic. This technique departs notably from current methods both in form and function. Rather than a closed-form model, or stochastic ...

  8. Motif-role-fingerprints: the building-blocks of motifs, clustering-coefficients and transitivities in directed networks.

    Directory of Open Access Journals (Sweden)

    Mark D McDonnell

    Full Text Available Complex networks are frequently characterized by metrics for which particular subgraphs are counted. One statistic from this category, which we refer to as motif-role fingerprints, differs from global subgraph counts in that the number of subgraphs in which each node participates is counted. As with global subgraph counts, it can be important to distinguish between motif-role fingerprints that are 'structural' (induced subgraphs and 'functional' (partial subgraphs. Here we show mathematically that a vector of all functional motif-role fingerprints can readily be obtained from an arbitrary directed adjacency matrix, and then converted to structural motif-role fingerprints by multiplying that vector by a specific invertible conversion matrix. This result demonstrates that a unique structural motif-role fingerprint exists for any given functional motif-role fingerprint. We demonstrate a similar result for the cases of functional and structural motif-fingerprints without node roles, and global subgraph counts that form the basis of standard motif analysis. We also explicitly highlight that motif-role fingerprints are elemental to several popular metrics for quantifying the subgraph structure of directed complex networks, including motif distributions, directed clustering coefficient, and transitivity. The relationships between each of these metrics and motif-role fingerprints also suggest new subtypes of directed clustering coefficients and transitivities. Our results have potential utility in analyzing directed synaptic networks constructed from neuronal connectome data, such as in terms of centrality. Other potential applications include anomaly detection in networks, identification of similar networks and identification of similar nodes within networks. Matlab code for calculating all stated metrics following calculation of functional motif-role fingerprints is provided as S1 Matlab File.

  9. Automatic translation of C/C++ parallel code into synchronous formalism using an SSA intermediate form

    OpenAIRE

    Besnard, Loïc; Gautier, Thierry; Moy, Matthieu; Talpin, Jean-Pierre; Johnson, Kenneth; Maraninchi, Florence

    2009-01-01

    We present an approach for the translation of imperative code (like C, C++) into the synchronous formalism \\signal, in order to use a model-checker to verify properties on the source code. The translation uses ßa\\ as an intermediate formalism, and the GCC compiler as a front-end. The contributions of this paper with respect to previous work are a more efficient translation scheme, and the management of parallel code. It is applied successfully on simple \\systemc\\ examples.

  10. Photoinduced C-C Cross-Coupling of Aryl Chlorides and Inert Arenes

    Directory of Open Access Journals (Sweden)

    Lele Wang

    2016-01-01

    Full Text Available Here we report a facile, efficient, and catalyst-free method to realize C-C cross-coupling of aryl chlorides and inert arenes under UV light irradiation. The aryl radical upon homolytic cleavage of C-Cl bond initiated the nucleophilic substitution reaction with inert arenes to give biaryl products. This mild reaction mode can also be applied to other synthetic reactions, such as the construction of C-N bonds and trifluoromethylated compounds.

  11. Design, manufacture and technological verification of SiC/C composite stirrer

    Directory of Open Access Journals (Sweden)

    A. Dolata-Grosz

    2009-09-01

    Full Text Available Purpose: In article were presented assumptions and choose results of investigations connected with material selection and technology production of prototype’s ceramic stirrer with destination to work in environment of liquid metal. In the research work the result of the design, manufacture and technological verification of SiC/C composite stirrer have been presented.Design/methodology/approach: The design of the stirrer (2D and 3D models and strength tests on the blade and fragment of the composite axle was prepared in the programme Solid Works and the FEM, using COSMOS software. Polymer infiltration and pyrolysis (PIP technique was used for fabrication SiC/C stirrer. Examination of wettability and suitability of the SiC/C composite for application in a liquid metal with sessile drop wettability was conducted. The surface geometry, conducted using a non-contact optical profilometer, FRT Micro’Prof.Findings: Further laboratory tests of the SiC/C composite stirrer, designed and developed in the Institute of Lightweight Engineering and Polymer Technology at TU Dresden have confirmed rightness of the design, assumptions regarding the thermal, mechanical and chemical resistance of the stirrer.Practical implications: The technological tests have proven a considerable reduction of the turbulence flow, which with an unchanged system of controlling the stirrer ensured stability of the liquid metal whirl and repeatability of the process.Originality/value: The application of this new material will enable not only the expansion of laboratory research, but it may also facilitate the implementation of liquid/phase technologies of obtaining MMC composites for the industry and thus, contribute to increasing the durability of stirrers in comparison with the solutions applied so far.

  12. Monte Carlo Simulation of Electron Swarms Parameters in c-C4F8/CF4 Gas Mixtures

    Institute of Scientific and Technical Information of China (English)

    LIU Xue-li; XIAO Deng-ming; WANG Yan-an; ZHANG Zhou-sheng

    2008-01-01

    The swarm parametes for c-C4F8/CF4 mixtures, including the density-normalized effective ionization coefficient, drift velocity and mean energy were calculated using Monte-Carlo method with the null collision technique. The overall density-reduced electric field strength could be varied between 150 and 500 Td,while the c-C4F8 content in gas mixtures is varied in the range of 0-100%. The value of the density-normalize deffective ionization coefficient shows a strong dependence on the c-C4F8 content, becoming more electronegative as the content of c-C4F8 is increased. The drift velocity of c-C4F4/CF4 mixtures is more affected by CF4. The calculated limiting field strength for c-C4F8/CF4 mixtures is higher than that of SF6/CF4.

  13. C-C chemokine receptor type five (CCR5: An emerging target for the control of HIV infection

    Directory of Open Access Journals (Sweden)

    Fatima Barmania

    2013-12-01

    Full Text Available When HIV was initially discovered as the causative agent of AIDS, many expected to find a vaccine within a few years. This has however proven to be elusive; it has been approximately 30 years since HIV was first discovered, and a suitable vaccine is still not in effect. In 2009, a paper published by Hutter et al. reported on a bone marrow transplant performed on an HIV positive individual using stem cells that were derived from a donor who was homozygous for a mutation in the CCR5 gene known as CCR5 delta-32 (Δ32 (Hütter et al., 2009. The HIV positive individual became HIV negative and remained free of viral detection after transplantation despite having halted anti-retroviral (ARV treatment. This review will focus on CCR5 as a key component in HIV immunity and will discuss the role of CCR5 in the control of HIV infection.

  14. Active Brazing of C/C Composite to Copper by AgCuTi Filler Metal

    Science.gov (United States)

    Zhang, Kexiang; Xia, Lihong; Zhang, Fuqin; He, Lianlong

    2016-05-01

    Brazing between the carbon-fiber-reinforced carbon composite (C/C composite) and copper has gained increasing interest because of its important application in thermal management systems in nuclear fusion reactors and in the aerospace industry. In order to examine the "interfacial shape effect" on the mechanical properties of the joint, straight and conical interfacial configurations were designed and machined on the surface of C/C composites before joining to copper using an Ag-68.8Cu-4.5Ti (wt pct) alloy. The microstructure and interfacial microchemistry of C/C composite/AgCuTi/Cu brazed joints were comprehensively investigated by using high-resolution transmission electron microscopy. The results indicate that the joint region of both straight and conical joints can be described as a bilayer. Reaction products of Cu3Ti3O and γ-TiO were formed near the copper side in a conical interface joint, while no reaction products were found in the straight case. The effect of Ag on the interfacial reaction was discussed, and the formation mechanism of the joints during brazing was proposed. On the basis of the detailed microstructure presented, the mechanical performance of the brazed joints was discussed in terms of reaction and morphology across the joint.

  15. A C/C++ Build System Based On Maven for the LHC Controls System

    CERN Document Server

    Nguyen Xuan, J; Dönszelmann, M

    2011-01-01

    The CERN accelerator controls system, mainly written in Java and C/C++, consists nowadays of 50 projects and 150 active developers. The controls group has decided to unify the development process and standards (e.g. project layout) using Apache Maven and Sonatype Nexus. Maven is the de-facto build tool for Java, it deals with versioning and dependency management, whereas Nexus is a repository manager. C/C++ developers were struggling to keep their dependencies on other CERN projects, as no versioning was applied, the libraries have to be compiled and available for several platforms and architectures, and finally there was no dependency management mechanism. This results in very complex Makefiles which were difficult to maintain. Even if Maven is primarily designed for Java, a plugin (Maven NAR) adapts the build process for native programming languages for different operating systems and platforms. However C/C++ developers were not keen to abandon their current Makefiles. Hence our approach was to combine the ...

  16. Determination of material properties for short fibre reinforced C/C-SiC

    Directory of Open Access Journals (Sweden)

    Hausherr J.-M.

    2015-01-01

    Full Text Available Determining the mechanical properties of short fibre reinforced CMC using standard sized coupons has always been a challenge due to a high statistical scattering of the measured values. Although the random orientation of short fibres results in a quasi-isotropic material behavior of 2D-structures with a sufficiently large volume, the small volume typical for test coupons usually results in a non-isotropic fibre orientation in the tested volume. This paper describes a method for manufacturing unidirectional oriented short fibre reinforced CMC materials and presents material properties of UD-C/C-SiC. After verifying the fibre orientation of the CMC using micro-computed tomography, coupons were extracted to determine the orthotropic material properties. These orthotropic material properties were then used to predict the properties of C/C-SiC with randomly distributed short fibres. To validate the method, micro-computed tomography is used to quantitatively determine the fibre orientation within coupons extracted from randomly distributed short fibre C/C-SiC. After mechanical three-point-bending tests, the measured stiffness and bending strength is compared with the predicted properties. Finally, the data are used to devise a method suited for reducing the inherent large spread of material properties associated with the measurement of CMC materials with randomly distributed short fibres.

  17. Structure of Leptin Receptor Related with Obesity

    DEFF Research Database (Denmark)

    Toleikis, Zigmantas

    The hormone leptin is central to obesity, but the molecular processes underlying the activation of the leptin receptor are unknown. To further the understanding of the system, an atomic resolution structure of this cytokine type I receptor in the unbound inactive form and in the activated bound...... receptor, while the D5 domain is the central leptin-binding domain, implicated in the first steps of activation. Both domains are characterized by a fibronectin type III fold and both contain a conserved WSXWS motif (X represents an unconserved amino acid residue), a distinct feature of the cytokine...... receptors. This motif is thought to play a major role in correct folding and activation of the receptor. The complex between leptin and the D5CA domain was analyzed using nuclear magnetic resonance spectroscopy and the amino acid residues implicated in the binding were determined. To investigate which parts...

  18. A structure filter for the Eukaryotic Linear Motif Resource

    Directory of Open Access Journals (Sweden)

    Gemünd Christine

    2009-10-01

    Full Text Available Abstract Background Many proteins are highly modular, being assembled from globular domains and segments of natively disordered polypeptides. Linear motifs, short sequence modules functioning independently of protein tertiary structure, are most abundant in natively disordered polypeptides but are also found in accessible parts of globular domains, such as exposed loops. The prediction of novel occurrences of known linear motifs attempts the difficult task of distinguishing functional matches from stochastically occurring non-functional matches. Although functionality can only be confirmed experimentally, confidence in a putative motif is increased if a motif exhibits attributes associated with functional instances such as occurrence in the correct taxonomic range, cellular compartment, conservation in homologues and accessibility to interacting partners. Several tools now use these attributes to classify putative motifs based on confidence of functionality. Results Current methods assessing motif accessibility do not consider much of the information available, either predicting accessibility from primary sequence or regarding any motif occurring in a globular region as low confidence. We present a method considering accessibility and secondary structural context derived from experimentally solved protein structures to rectify this situation. Putatively functional motif occurrences are mapped onto a representative domain, given that a high quality reference SCOP domain structure is available for the protein itself or a close relative. Candidate motifs can then be scored for solvent-accessibility and secondary structure context. The scores are calibrated on a benchmark set of experimentally verified motif instances compared with a set of random matches. A combined score yields 3-fold enrichment for functional motifs assigned to high confidence classifications and 2.5-fold enrichment for random motifs assigned to low confidence classifications

  19. Predicting novel binding modes of agonists to β adrenergic receptors using all-atom molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Stefano Vanni

    Full Text Available Understanding the binding mode of agonists to adrenergic receptors is crucial to enabling improved rational design of new therapeutic agents. However, so far the high conformational flexibility of G protein-coupled receptors has been an obstacle to obtaining structural information on agonist binding at atomic resolution. In this study, we report microsecond classical molecular dynamics simulations of β(1 and β(2 adrenergic receptors bound to the full agonist isoprenaline and in their unliganded form. These simulations show a novel agonist binding mode that differs from the one found for antagonists in the crystal structures and from the docking poses reported by in silico docking studies performed on rigid receptors. Internal water molecules contribute to the stabilization of novel interactions between ligand and receptor, both at the interface of helices V and VI with the catechol group of isoprenaline as well as at the interface of helices III and VII with the ethanolamine moiety of the ligand. Despite the fact that the characteristic N-C-C-OH motif is identical in the co-crystallized ligands and in the full agonist isoprenaline, the interaction network between this group and the anchor site formed by Asp(3.32 and Asn(7.39 is substantially different between agonists and inverse agonists/antagonists due to two water molecules that enter the cavity and contribute to the stabilization of a novel network of interactions. These new binding poses, together with observed conformational changes in the extracellular loops, suggest possible determinants of receptor specificity.

  20. PH motifs in PAR1&2 endow breast cancer growth.

    Science.gov (United States)

    Kancharla, A; Maoz, M; Jaber, M; Agranovich, D; Peretz, T; Grisaru-Granovsky, S; Uziely, B; Bar-Shavit, R

    2015-01-01

    Although emerging roles of protease-activated receptor1&2 (PAR1&2) in cancer are recognized, their underlying signalling events are poorly understood. Here we show signal-binding motifs in PAR1&2 that are critical for breast cancer growth. This occurs via the association of the pleckstrin homology (PH) domain with Akt/PKB as a key signalling event of PARs. Other PH-domain signal-proteins such as Etk/Bmx and Vav3 also associate with PAR1 and PAR2 through their PH domains. PAR1 and PAR2 bind with priority to Etk/Bmx. A point mutation in PAR2, H349A, but not in R352A, abrogates PH-protein association and is sufficient to markedly reduce PAR2-instigated breast tumour growth in vivo and placental extravillous trophoblast (EVT) invasion in vitro. Similarly, the PAR1 mutant hPar1-7A, which is unable to bind the PH domain, reduces mammary tumours and EVT invasion, endowing these motifs with physiological significance and underscoring the importance of these previously unknown PAR1 and PAR2 PH-domain-binding motifs in both pathological and physiological invasion processes. PMID:26600192

  1. SLIDER: Mining correlated motifs in protein-protein interaction networks

    NARCIS (Netherlands)

    Boyen, P.; Dijk, van A.D.J.; Ham, van R.C.H.J.; Neven, F.

    2009-01-01

    Abstract—Correlated motif mining (CMM) is the problem to find overrepresented pairs of patterns, called motif pairs, in interacting protein sequences. Algorithmic solutions for CMM thereby provide a computational method for predicting binding sites for protein interaction. In this paper, we adopt a

  2. BlockLogo: Visualization of peptide and sequence motif conservation

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Kudahl, Ulrich Johan; Simon, Christian;

    2013-01-01

    BlockLogo is a web-server application for the visualization of protein and nucleotide fragments, continuous protein sequence motifs, and discontinuous sequence motifs using calculation of block entropy from multiple sequence alignments. The user input consists of a multiple sequence alignment, se...

  3. Aztec, Incan and Mayan Motifs...Lead to Distinctive Designs.

    Science.gov (United States)

    Shields, Joanne

    2001-01-01

    Describes an art project for seventh-grade students in which they choose motifs based on Incan, Aztec, and Mayan Indian materials to incorporate into two-dimensional designs. Explains that the activity objective is to create a unified, balanced and pleasing composition using a minimum of three motifs. (CMK)

  4. The phenomenon of astral motifs on late mediaeval tombstones

    Science.gov (United States)

    Mijatović, V.; Ninković, S.; Vemić, D.

    2003-10-01

    The authors study astral motifs present on some mediaeval tombstones found in present-day Serbia and Montenegro and in the neighbouring countries (especially in Bosnia and Herzegovina). The authors discern some important astral motifs, explain them and present a short review concerning their frequency.

  5. Probing structural changes of self assembled i-motif DNA

    KAUST Repository

    Lee, Iljoon

    2015-01-01

    We report an i-motif structural probing system based on Thioflavin T (ThT) as a fluorescent sensor. This probe can discriminate the structural changes of RET and Rb i-motif sequences according to pH change. This journal is

  6. The effect of orthology and coregulation on detecting regulatory motifs.

    Directory of Open Access Journals (Sweden)

    Valerie Storms

    Full Text Available BACKGROUND: Computational de novo discovery of transcription factor binding sites is still a challenging problem. The growing number of sequenced genomes allows integrating orthology evidence with coregulation information when searching for motifs. Moreover, the more advanced motif detection algorithms explicitly model the phylogenetic relatedness between the orthologous input sequences and thus should be well adapted towards using orthologous information. In this study, we evaluated the conditions under which complementing coregulation with orthologous information improves motif detection for the class of probabilistic motif detection algorithms with an explicit evolutionary model. METHODOLOGY: We designed datasets (real and synthetic covering different degrees of coregulation and orthologous information to test how well Phylogibbs and Phylogenetic sampler, as representatives of the motif detection algorithms with evolutionary model performed as compared to MEME, a more classical motif detection algorithm that treats orthologs independently. RESULTS AND CONCLUSIONS: Under certain conditions detecting motifs in the combined coregulation-orthology space is indeed more efficient than using each space separately, but this is not always the case. Moreover, the difference in success rate between the advanced algorithms and MEME is still marginal. The success rate of motif detection depends on the complex interplay between the added information and the specificities of the applied algorithms. Insights in this relation provide information useful to both developers and users. All benchmark datasets are available at http://homes.esat.kuleuven.be/~kmarchal/Supplementary_Storms_Valerie_PlosONE.

  7. MotifCombinator: a web-based tool to search for combinations of cis-regulatory motifs

    Directory of Open Access Journals (Sweden)

    Tsunoda Tatsuhiko

    2007-03-01

    Full Text Available Abstract Background A combination of multiple types of transcription factors and cis-regulatory elements is often required for gene expression in eukaryotes, and the combinatorial regulation confers specific gene expression to tissues or environments. To reveal the combinatorial regulation, computational methods are developed that efficiently infer combinations of cis-regulatory motifs that are important for gene expression as measured by DNA microarrays. One promising type of computational method is to utilize regression analysis between expression levels and scores of motifs in input sequences. This type takes full advantage of information on expression levels because it does not require that the expression level of each gene be dichotomized according to whether or not it reaches a certain threshold level. However, there is no web-based tool that employs regression methods to systematically search for motif combinations and that practically handles combinations of more than two or three motifs. Results We here introduced MotifCombinator, an online tool with a user-friendly interface, to systematically search for combinations composed of any number of motifs based on regression methods. The tool utilizes well-known regression methods (the multivariate linear regression, the multivariate adaptive regression spline or MARS, and the multivariate logistic regression method for this purpose, and uses the genetic algorithm to search for combinations composed of any desired number of motifs. The visualization systems in this tool help users to intuitively grasp the process of the combination search, and the backup system allows users to easily stop and restart calculations that are expected to require large computational time. This tool also provides preparatory steps needed for systematic combination search – i.e., selecting single motifs to constitute combinations and cutting out redundant similar motifs based on clustering analysis. Conclusion

  8. The formation and characteristics of the i-motif structure within the promoter of the c-myb proto-oncogene.

    Science.gov (United States)

    Li, Huihui; Hai, Jinhui; Zhou, Jiang; Yuan, Gu

    2016-09-01

    C-myb proto-oncogene is a potential therapeutic target for some human solid tumors and leukemias. A long cytosine-rich sequence, which locates the downstream of the transcription initiation site, is demonstrated to fold into an intramolecular i-motif DNA using electrospray ionization mass spectrometry (ESI-MS) and circular dichroism (CD) spectroscopy. Effects of factors, including the pH value, the number of C:C(+) dimers, the concentration of buffer, the molecular crowding condition, and the coexistence of the complementary DNA, on the formation and the structural stability of the i-motif DNA are systematically studied. We have demonstrated that the i-motif folding in the c-myb promoter could be accelerated upon synergistic physiological stimuli including intracellular molecular crowding and low pH values, as well as the large number of the i-motif C:C(+) dimers. Meanwhile, various inputs, such as acids/bases and metal ions, have exhibited their abilities in controlling the conformational switch of the c-myb GC-rich DNA. Acidic pH values and the presence of K(+) ions can induce the dissociation of the double helix. Our present strategy can greatly extend the potential usages of i-motif DNA molecules with specific sequences as conformational switch-controlled devices. Moreover, this work demonstrates the superiority of CD spectroscopy associated with ESI-MS as a rapid, more cost-effective and sensitive structural change responsive method in the research of DNA conformational switching. PMID:27487467

  9. An algorithm for motif-based network design

    CERN Document Server

    Mäki-Marttunen, Tuomo

    2016-01-01

    A determinant property of the structure of a biological network is the distribution of local connectivity patterns, i.e., network motifs. In this work, a method for creating directed, unweighted networks while promoting a certain combination of motifs is presented. This motif-based network algorithm starts with an empty graph and randomly connects the nodes by advancing or discouraging the formation of chosen motifs. The in- or out-degree distribution of the generated networks can be explicitly chosen. The algorithm is shown to perform well in producing networks with high occurrences of the targeted motifs, both ones consisting of 3 nodes as well as ones consisting of 4 nodes. Moreover, the algorithm can also be tuned to bring about global network characteristics found in many natural networks, such as small-worldness and modularity.

  10. Dynamic Motifs of Strategies in Prisoner's Dilemma Games

    CERN Document Server

    Kim, Young Jin; Jeong, Seon-Young; Son, Seung-Woo

    2014-01-01

    We investigate the win-lose relations between strategies of iterated prisoner's dilemma games by using a directed network concept to display the replicator dynamics results. In the giant strongly-connected component of the win/lose network, we find win-lose circulations similar to rock-paper-scissors and analyze the fixed point and its stability. Applying the network motif concept, we introduce dynamic motifs, which describe the population dynamics relations among the three strategies. Through exact enumeration, we find 22 dynamic motifs and display their phase portraits. Visualization using directed networks and motif analysis is a useful method to make complex dynamic behavior simple in order to understand it more intuitively. Dynamic motifs can be building blocks for dynamic behavior among strategies when they are applied to other types of games.

  11. Discovering multiple realistic TFBS motifs based on a generalized model

    Directory of Open Access Journals (Sweden)

    Leung Kwong-Sak

    2009-10-01

    Full Text Available Abstract Background Identification of transcription factor binding sites (TFBSs is a central problem in Bioinformatics on gene regulation. de novo motif discovery serves as a promising way to predict and better understand TFBSs for biological verifications. Real TFBSs of a motif may vary in their widths and their conservation degrees within a certain range. Deciding a single motif width by existing models may be biased and misleading. Additionally, multiple, possibly overlapping, candidate motifs are desired and necessary for biological verification in practice. However, current techniques either prohibit overlapping TFBSs or lack explicit control of different motifs. Results We propose a new generalized model to tackle the motif widths by considering and evaluating a width range of interest simultaneously, which should better address the width uncertainty. Moreover, a meta-convergence framework for genetic algorithms (GAs, is proposed to provide multiple overlapping optimal motifs simultaneously in an effective and flexible way. Users can easily specify the difference amongst expected motif kinds via similarity test. Incorporating Genetic Algorithm with Local Filtering (GALF for searching, the new GALF-G (G for generalized algorithm is proposed based on the generalized model and meta-convergence framework. Conclusion GALF-G was tested extensively on over 970 synthetic, real and benchmark datasets, and is usually better than the state-of-the-art methods. The range model shows an increase in sensitivity compared with the single-width ones, while providing competitive precisions on the E. coli benchmark. Effectiveness can be maintained even using a very small population, exhibiting very competitive efficiency. In discovering multiple overlapping motifs in a real liver-specific dataset, GALF-G outperforms MEME by up to 73% in overall F-scores. GALF-G also helps to discover an additional motif which has probably not been annotated in the dataset

  12. De Novo Regulatory Motif Discovery Identifies Significant Motifs in Promoters of Five Classes of Plant Dehydrin Genes.

    Science.gov (United States)

    Zolotarov, Yevgen; Strömvik, Martina

    2015-01-01

    Plants accumulate dehydrins in response to osmotic stresses. Dehydrins are divided into five different classes, which are thought to be regulated in different manners. To better understand differences in transcriptional regulation of the five dehydrin classes, de novo motif discovery was performed on 350 dehydrin promoter sequences from a total of 51 plant genomes. Overrepresented motifs were identified in the promoters of five dehydrin classes. The Kn dehydrin promoters contain motifs linked with meristem specific expression, as well as motifs linked with cold/dehydration and abscisic acid response. KS dehydrin promoters contain a motif with a GATA core. SKn and YnSKn dehydrin promoters contain motifs that match elements connected with cold/dehydration, abscisic acid and light response. YnKn dehydrin promoters contain motifs that match abscisic acid and light response elements, but not cold/dehydration response elements. Conserved promoter motifs are present in the dehydrin classes and across different plant lineages, indicating that dehydrin gene regulation is likely also conserved.

  13. Use of a C.C.D. array in an X-ray pinhole camera

    International Nuclear Information System (INIS)

    X-ray imaging adapted to the laser-matter interaction experiments consits in recording plasma images from its X-ray emission; those phenomena have between 100 ps and some nanoseconds duration. When we only need spatial information on 1-10 keV X-ray emission, the most simple imaging device is the pinhole camera; the two dimension image of the plasma is temporally integrated by an X-ray sensitive detector. Until now, X-ray film was used. Its operation and processing were long and tedious, so we replaced it by a television camera built around a Charge Coupled device (C.C.D.). This camera is directly integrated in the pinhole camera. The X-ray detection is made by the silicon substrat of a C.C.D. without input window working in the vacuum of the experiment chamber; a compact camera head (40 mm diameter, 120 mm length) located near the C.C.D. (1 to 2 cm) makes the charge voltage conversion and the signal amplification. The immediate operation of images is done by an image acquisition and processing unit after digitizing the video signal on 8 bits. From measurements made on a continuous X-ray source (5,4 keV) we could point out the fact that a THOMSON-CSF THX 31135 CCD is 10 times more sensitive than the X-ray SB2 KODAK film that we use in pinhole cameras. The dynamic range measured in these conditions was about 300. The first experimental results obtained on a pulsed X-ray source are presented

  14. Long-term tropospheric trend of octafluorocyclobutane (c-C4F8 or PFC-318

    Directory of Open Access Journals (Sweden)

    T. Röckmann

    2011-07-01

    Full Text Available Air samples collected at Cape Grim, Tasmania between 1978 and 2008 and during a series of more recent aircraft sampling programmes have been analysed to determine the atmospheric abundance and trend of octafluorocyclobutane (-C4F8 or PFC-318. c-C4F8 has an atmospheric lifetime in excess of 3000 yr and a global warming potential (GWP of 10 300 (100 yr time horizon, making it one of the most potent greenhouse gases detected in the atmosphere to date. The abundance of c-C4F8 in the Southern Hemisphere has risen from 0.35 ppt in 1978 to 1.2 ppt in 2010, and is currently increasing at a rate of around 0.03 ppt yr−1. It is the third most abundant perfluorocarbon (PFC in the present day atmosphere, behind CF4 (~75 ppt and C2F6 (~4 ppt. The origin of c-C4F8 is unclear. Using a 2-D global model to derive top-down global emissions based on the Cape Grim measurements yields a recent (2007 emission rate of around 1.1 Gg yr−1 and a cumulative emission up to and including 2007 of 38.1 Gg. Emissions reported on the EDGAR emissions database for the period 1986–2005 represent less than 1 % of the top-down emissions for the same period, which suggests there is a large unaccounted for source of this compound. It is also apparent that the magnitude of this source has varied considerably over the past 30 yr, declining sharply in the late 1980s before increasing again in the mid-1990s.

  15. A C/C++ build system based on Maven for the LHC control system

    International Nuclear Information System (INIS)

    The CERN accelerator control system, mainly written in Java and C/C++, consists nowadays of 50 projects and 150 active developers. The controls group has decided to unify the development process and standards (e.g. project layout) using Apache Maven and Sonatype Nexus. Maven is de-facto a build tool for Java, it deals with versioning and dependency management, whereas Nexus is a repository manager. C/C++ developers were struggling to keep their dependencies on other CERN projects, as no versioning was applied, the libraries have to be compiled and available for several platforms and architectures, and finally there was no dependency management mechanism. This results in very complex Make-files which were difficult to maintain. Even if Maven is primarily designed for Java, a plug-in (Maven NAR) adapts the build process for native programming languages for different operating systems and platforms. However C/C++ developers were not keen to abandon their current Make-files. Hence our approach was to combine the best of the 2 worlds: NAR/Nexus and Make-files. Maven NAR manages the dependencies, the versioning and creates a file with the linker and compiler options to include the dependencies. The Make-files carry the build process to generate the binaries. Finally the resulting artifacts (binaries, header files, metadata) are versioned and stored in a central Nexus repository. Early experiments were conducted in the scope of the control group's Testbed. Some existing projects have been successfully converted to this solution and some starting projects use this implementation. (authors)

  16. Photoinduced C-C bond cleavage via electron-transfer reactions: visible-light-mediated scission of tertiary amines

    Energy Technology Data Exchange (ETDEWEB)

    Lee, L.Y.C.; Ci, X.; Giannotti, C.; Whitten, D.G.

    1986-01-08

    This paper reports the electron-transfer photochemistry of some substituted tertiary amines that contain potentially labile C-C bonds adjacent to the amine. Results are presented which indicate that photoinduced electron transfer can lead to reactions in which the net process involves use of visible light to mediate selective cleavage of C-C bonds to produce radicals. 34 references.

  17. Measurement of Swarm Parameters of c-C4F8/CO2 and Its Insulation Characteristics Analysis

    Institute of Scientific and Technical Information of China (English)

    ZHANG Liu-chun; XIAO Deng-ming; ZHANG Dong; WU Bian-tao

    2008-01-01

    In c-C4F8 and c-C4F8/CO2 mixtures, the swarm parameters including ionization coefficient, attachment coefficient and effective ionization coefficient were obtained at the ratio of the electric field strength to the gas density between 150-550 Td by the steady-state Townsend (SST) method. Static breakdown voltages at each ratio were also measured at the SST condition. The limiting field strengths were obtained by two methods:computing the density-normalized effective ionization coefficient as a function of the overall density-reduced electric field strength; and measuring static breakdown voltages as a function of the product of gas density and electrode separation. Good agreement was obtained by these two methods, which ensures the correctness of the former method. The limiting field strengths of c-C4F8 and c-C4F8/CO2 mixtures were compared with those ofpure SF6, SF6/CO2 mixtures and pure c-C4Fs. It is found that buffer gas CO2 does not reduce the limiting field strengths of c-C4F8 greatly, the limiting field strengths of c-C4F8/CO2 mixtures are higher than those of SF6/CO2 mixtures or even pure SF6, and so c-C4F8/CO2 mixtures are suggested to be possible substitutes for SF6.

  18. The most common mutation of KRT9, c.C487T (p.R163W), in epidermolytic palmoplantar keratoderma in two large Chinese pedigrees.

    Science.gov (United States)

    Liu, Wen-Ting; Ke, Hai-Ping; Zhao, Yan; Chen, Xiao-Ling; Lu, Jia-Jun; Du, Zheng-Fang; Yu, Dan; Zhang, Xian-Ning

    2012-04-01

    Epidermolytic palmoplantar keratoderma (EPPK) is generally associated with dominant-negative mutations of the Keratin 9 gene (KRT9), and rarely with the Keratin 1 gene (KRT1). To date, a myriad of mutations has been reported with a high frequency of codon 163 mutations within the first exon of KRT9 in different populations. Notably, a distinct phenotypic heterogeneity, digital mutilation, was found recently in a 58-year-old female Japanese EPPK patient with p.R163W. Here, we report the most common mutation, c.C487T (p.R163W) of KRT9, in two large EPPK pedigrees from southeast China. The arginine residue in peptide position 163 remains almost constant in at least 47 intermediate filament proteins ranging from snail to human. A substitution in arginine alters both the charge and shape of the 1A rod domain and disrupts the function of the helix initiation motif of keratins, finally compromising the integrity of filaments and weakening their stability in the epidermis of palms and soles. We summarize the clinical symptoms of EPPK in Chinese and show that knuckle pads are associated with KRT9 mutations. We suggest that the frequency of p.R163W in Chinese EPPK patients (31.03%) is consistent with that in the general population (29.33%), and that codon 163 is truly a hotspot mutational site of KRT9.

  19. Homolytic Bond Dissociation Enthalpies of C C and C-H Bonds in Highly Crowded Alkanes

    Institute of Scientific and Technical Information of China (English)

    ZHU Chen; RUI Lei; FU Yao

    2008-01-01

    The homolytic C-C and C--H bond dissociation enthalpyies (BDE) of highly crowded alkanes were calcu- lated by using an ONIOM-G3B3 method. Geometric parameters such as bond length, bond angle and molecular volume were carefully investigated, as most of the acyclic alkanes in this study were not yet synthesized. These pa-rameters reflect the influence of steric effect on BDE. Good correlations were found between the rapid decrease of BDE and the increase of molecular volumes. The correlations can be applied to the prediction of the possible exis-tence of many highly strained compounds.

  20. Study of dielectron production in C+C collisions at 1 AGeV

    CERN Document Server

    Agakichiev, G; Pol, H Alvarez; Balanda, A; Bassini, R; Bellia, G; Belver, D; Belyaev, A; Blanco, A; Boehmer, M; Bortolotti, A; Boyard, J L; Braun-Munzinger, P; Cabanelas, P; Castro, E; Christ, T; Destefanis, M; Díaz, J; Dohrmann, F; Dybczak, A; Eberl, T; Fabbietti, L; Finocchiaro, P; Fonte, Paulo J R; Friese, J; Fröhlich, I; Galatyuk, T; Garzón, J A; Gernhäuser, R; Gil, A; Gilardi, C; Golubeva, M; Diaz, D Gonzalez; Grosse, E; Guber, F; Heilmann, M; Hennino, T; Holzmann, R; Ierusalimov, A; Iori, I; Ivashkin, A; Jurkovic, M; Kämpfer, B; Kanaki, K; Karavicheva, T; Kirschner, D; König, I; König, W; Kolb, B W; Kotte, R; Kozuch, A; Krasa, A; Krizek, F; Krücken, R; Kühn, W; Kugler, A; Kurepin, A; Valverde, J Lamas; Lang, S; Lange, J S; Lapidus, K; Lopes, L; Maier, L; Mangiarotti, A; Marin, J; Markert, J; Metag, V; Michalska, B; Mishra, D; Moriniere, E; Mousa, J; Münch, M; Müntz, C; Naumann, Lutz; Novotny, R; Otwinowski, J; Pachmayer, Y C; Palka, M; Parpottas, Y; Pechenov, V; Pechenova, O; Perez, T; Pietraszko, J; Pleskac, R; Przygoda, W; Ramstein, B; Reshetin, A; Stephan, M Roy; Rustamov, A; Sadovskii, A; Sailer, B; Salabura, P; Schmah, A; Simon, R; Sobolev, Y; Spataro, S; Spruck, B; Ströbele, H; Stroth, J; Sturm, C; Sudol, M; Tarantola, A; Teilab, K; Tlustý, P; Toia, A; Traxler, M; Trebacz, R; Tsertos, H; Veretenkin, I; Wagner, V; Weber, M; Wen, H; Wisniowski, M; Wojcik, T; Wüstenfeld, J; Yurevich, S; Zanevsky, Y; Zhou, P; Zumbruch, P

    2007-01-01

    The emission of e+e- pairs from C+C collisions at an incident energy of 1 GeV per nucleon has been investigated. The measured production probabilities, spanning from the pi0-Dalitz to the rho/omega! invariant-mass region, display a strong excess above the cocktail of standard hadronic sources. The bombarding-energy dependence of this excess is found to scale like pion production, rather than like eta production. The data are in good agreement with results obtained in the former DLS experiment.

  1. Study of dielectron production in C+C collisions at 1A GeV

    International Nuclear Information System (INIS)

    The emission of e+e- pairs from C+C collisions at an incident energy of 1 GeV per nucleon has been investigated. The measured production probabilities, spanning from the π0-Dalitz to the ρ/ω invariant-mass region, display a strong excess above the cocktail of standard hadronic sources. The bombarding-energy dependence of this excess is found to scale like pion production, rather than like eta production. The data are in good agreement with results obtained in the former DLS experiment

  2. Study of dielectron production in C+C collisions at 1A GeV

    Energy Technology Data Exchange (ETDEWEB)

    Agakishiev, G. [II.Physikalisches Institut, Justus Liebig Universitaet Giessen, 35392 Giessen (Germany); Agodi, C. [Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali del Sud, 95125 Catania (Italy); Alvarez-Pol, H. [Departamento de Fisica de Particulas, University of Santiago de Compostela, 15782 Santiago de Compostela (Spain); Balanda, A. [Smoluchowski Institute of Physics, Jagiellonian University of Cracow, 30-059 Krakow (Poland); Also at Panstwowa Wyzsza Szkola Zawodowa, 33-300 Nowy Sacz (Poland); Bassini, R. [Istituto Nazionale di Fisica Nucleare, Sezione di Milano, 20133 Milano (Italy); Bellia, G. [Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali del Sud, 95125 Catania (Italy); Also at Dipartimento di Fisica e Astronomia, Universita di Catania, 95125 Catania (Italy); Belver, D. [Departamento de Fisica de Particulas, University of Santiago de Compostela, 15782 Santiago de Compostela (Spain); Belyaev, A. [Joint Institute of Nuclear Research, 141980 Dubna (Russian Federation); Blanco, A. [LIP-Laboratorio de Instrumentacao e Fisica Experimental de Particulas, 3004-516 Coimbra (Portugal); Boehmer, M. [Physik Department E12, Technische Universitaet Muenchen, 85748 Muenchen (Germany); Bortolotti, A. [Istituto Nazionale di Fisica Nucleare, Sezione di Milano, 20133 Milano (Italy); Boyard, J.L. [Institut de Physique Nucleaire (UMR 8608), CNRS/IN2P3 - UniversitT Paris Sud, F-91406 Orsay cedex (France); Braun-Munzinger, P. [Gesellschaft fuer Schwerionenforschung mbH, 64291 Darmstadt (Germany); Cabanelas, P.; Castro, E. [Departamento de Fisica de Particulas, University of Santiago de Compostela, 15782 Santiago de Compostela (Spain); Chernenko, S. [Joint Institute of Nuclear Research, 141980 Dubna (Russian Federation); Christ, T. [Physik Department E12, Technische Universitaet Muenchen, 85748 Muenchen (Germany); Destefanis, M. [II.Physikalisches Institut, Justus Liebig Universitaet Giessen, 35392 Giessen (Germany)] (and others)

    2008-05-15

    The emission of e{sup +}e{sup -} pairs from C+C collisions at an incident energy of 1 GeV per nucleon has been investigated. The measured production probabilities, spanning from the {pi}{sup 0}-Dalitz to the {rho}/{omega} invariant-mass region, display a strong excess above the cocktail of standard hadronic sources. The bombarding-energy dependence of this excess is found to scale like pion production, rather than like eta production. The data are in good agreement with results obtained in the former DLS experiment.

  3. Transition metal catalysed functionalisation of c=c through boron chemistry: a tandem approach

    OpenAIRE

    Lillo García, Vanesa

    2009-01-01

    Organoboron compounds are some of the most useful reagents in organic synthesis. The carbon-boron bond, once formed, can be cleaved in a variety of ways, with or without homologation, leading to a wide range of useful functional groups. The catalytic addition of H-B or B-B across to unsaturated C-C bond is one of the catalytic processes with higher selective control in the C-B bond formation. In the first Chapter of this thesis shows the evolution through the literature of the three main cat...

  4. Superconductivity and the b.c.c. to A-15 transformation in Nb-Au alloys

    International Nuclear Information System (INIS)

    Nb-Au alloys near the composition Nb3Au can be quenched from the high temperature α solid solution phase field, retaining the b.c.c. structure. Results are reported on their superconducting, mechanical and physical properties as a function of composition. Short low temperature anneals transform these materials to the equilibrium A-15 structure with Tsub(c) up to 11 K. Results are reported on the superconducting and physical properties of the transformed A-15 structure materials and the way in which the properties of the transformed materials are affected by annealing temperature and time is described. (author)

  5. An erbium-based bifuctional heterogeneous catalyst: a cooperative route towards C-C bond formation.

    Science.gov (United States)

    Oliverio, Manuela; Costanzo, Paola; Macario, Anastasia; De Luca, Giuseppina; Nardi, Monica; Procopio, Antonio

    2014-07-15

    Heterogeneous bifuctional catalysts are multifunctional synthetic catalysts enabling efficient organic transformations by exploiting two opposite functionalities without mutual destruction. In this paper we report the first Er(III)-based metallorganic heterogeneous catalyst, synthesized by post-calcination MW-assisted grafting and modification of the natural aminoacid L-cysteine. The natural acid-base distance between sites was maintained to assure the cooperation. The applicability of this new bifunctional heterogeneous catalyst to C-C bond formation and the supposed mechanisms of action are discussed as well.

  6. An Erbium-Based Bifuctional Heterogeneous Catalyst: A Cooperative Route Towards C-C Bond Formation

    Directory of Open Access Journals (Sweden)

    Manuela Oliverio

    2014-07-01

    Full Text Available Heterogeneous bifuctional catalysts are multifunctional synthetic catalysts enabling efficient organic transformations by exploiting two opposite functionalities without mutual destruction. In this paper we report the first Er(III-based metallorganic heterogeneous catalyst, synthesized by post-calcination MW-assisted grafting and modification of the natural aminoacid L-cysteine. The natural acid–base distance between sites was maintained to assure the cooperation. The applicability of this new bifunctional heterogeneous catalyst to C-C bond formation and the supposed mechanisms of action are discussed as well.

  7. SiC/C nanocable structure produced in silicon carbide by arc plasma heating

    Science.gov (United States)

    Nayak, B. B.

    2012-01-01

    Defect-free and long SiC/C nanocables have been produced by heating SiC powder at 3000°C by employing dc arc plasma (Ar) in a specially designed configuration of graphite arc. Microstructural characterizations of the heat-treated powder carried out by TEM, HRTEM, SAED, EDS, and micro Raman spectroscopy showed the nanocables to consist of a SiC shell/sheath stuffed with wire type solid C core. A possible mechanism is discussed to explain the cable-type growth.

  8. Metalloenzyme-Like Zeolites as Lewis Acid Catalysts for C-C Bond Formation.

    Science.gov (United States)

    Van de Vyver, Stijn; Román-Leshkov, Yuriy

    2015-10-19

    The use of metalloenzyme-like zeolites as Lewis acid catalysts for C-C bond formation reactions has received increasing attention over the past few years. In particular, the observation of direct aldol condensation reactions enabled by hydrophobic zeolites with isolated framework metal sites has encouraged the development of catalytic approaches for producing chemicals from biomass-derived compounds. The discovery of new Diels-Alder cycloaddition/dehydration routes and experimental and computational studies of Lewis acid catalyzed carbonyl-ene reactions have given a further boost to this rapidly evolving field. PMID:26465652

  9. GEOS-C C-band transponder prelaunch calibration and test data

    Science.gov (United States)

    Selser, A. R.

    1976-01-01

    The delay characteristics and spacecraft telemetry housekeeping data for the GEOS-C C-Band transponders are presented. The data are presented in graphical form to provide a convenient method for computing radar range measurement corrections as a function of signal strength at the transponder and spacecraft environment. The data are also presented in tabular form along with the mathematical models used to derive the curves. Also included are a list of the operating characteristics of each transponder and a description of the calibration test equipment set-up.

  10. Microanalysis on the Hydrogen Ion Irradiated 50 wt pct TiC-C Films

    Institute of Scientific and Technical Information of China (English)

    Hui JIANG; Yaoguang LIU; Ningkang HUANG

    2007-01-01

    The 50 wt pct TiC-C films were prepared on stainless steel substrates by using a technique of ion beam mixing.These films were irradiated by hydrogen ion beam with a dose of 1×1018 ions/cm2 and an energy of 5 keV.Microanalysis of X-ray photoelectron spectroscopy (XPS) and secondary ion mass spectroscopy (SIMS) were used to analyze the films before and after hydrogen ion irradiation and to study the mechanism of hydrogen resistance.

  11. Computational analyses of synergism in small molecular network motifs.

    Directory of Open Access Journals (Sweden)

    Yili Zhang

    2014-03-01

    Full Text Available Cellular functions and responses to stimuli are controlled by complex regulatory networks that comprise a large diversity of molecular components and their interactions. However, achieving an intuitive understanding of the dynamical properties and responses to stimuli of these networks is hampered by their large scale and complexity. To address this issue, analyses of regulatory networks often focus on reduced models that depict distinct, reoccurring connectivity patterns referred to as motifs. Previous modeling studies have begun to characterize the dynamics of small motifs, and to describe ways in which variations in parameters affect their responses to stimuli. The present study investigates how variations in pairs of parameters affect responses in a series of ten common network motifs, identifying concurrent variations that act synergistically (or antagonistically to alter the responses of the motifs to stimuli. Synergism (or antagonism was quantified using degrees of nonlinear blending and additive synergism. Simulations identified concurrent variations that maximized synergism, and examined the ways in which it was affected by stimulus protocols and the architecture of a motif. Only a subset of architectures exhibited synergism following paired changes in parameters. The approach was then applied to a model describing interlocked feedback loops governing the synthesis of the CREB1 and CREB2 transcription factors. The effects of motifs on synergism for this biologically realistic model were consistent with those for the abstract models of single motifs. These results have implications for the rational design of combination drug therapies with the potential for synergistic interactions.

  12. Triadic motifs in the dependence networks of virtual societies

    Science.gov (United States)

    Xie, Wen-Jie; Li, Ming-Xia; Jiang, Zhi-Qiang; Zhou, Wei-Xing

    2014-06-01

    In friendship networks, individuals have different numbers of friends, and the closeness or intimacy between an individual and her friends is heterogeneous. Using a statistical filtering method to identify relationships about who depends on whom, we construct dependence networks (which are directed) from weighted friendship networks of avatars in more than two hundred virtual societies of a massively multiplayer online role-playing game (MMORPG). We investigate the evolution of triadic motifs in dependence networks. Several metrics show that the virtual societies evolved through a transient stage in the first two to three weeks and reached a relatively stable stage. We find that the unidirectional loop motif (M9) is underrepresented and does not appear, open motifs are also underrepresented, while other close motifs are overrepresented. We also find that, for most motifs, the overall level difference of the three avatars in the same motif is significantly lower than average, whereas the sum of ranks is only slightly larger than average. Our findings show that avatars' social status plays an important role in the formation of triadic motifs.

  13. Profile-based short linear protein motif discovery

    Directory of Open Access Journals (Sweden)

    Haslam Niall J

    2012-05-01

    Full Text Available Abstract Background Short linear protein motifs are attracting increasing attention as functionally independent sites, typically 3–10 amino acids in length that are enriched in disordered regions of proteins. Multiple methods have recently been proposed to discover over-represented motifs within a set of proteins based on simple regular expressions. Here, we extend these approaches to profile-based methods, which provide a richer motif representation. Results The profile motif discovery method MEME performed relatively poorly for motifs in disordered regions of proteins. However, when we applied evolutionary weighting to account for redundancy amongst homologous proteins, and masked out poorly conserved regions of disordered proteins, the performance of MEME is equivalent to that of regular expression methods. However, the two approaches returned different subsets within both a benchmark dataset, and a more realistic discovery dataset. Conclusions Profile-based motif discovery methods complement regular expression based methods. Whilst profile-based methods are computationally more intensive, they are likely to discover motifs currently overlooked by regular expression methods.

  14. The interleukin-4 receptor: signal transduction by a hematopoietin receptor.

    Science.gov (United States)

    Keegan, A D; Pierce, J H

    1994-02-01

    Over the last several years, the receptors for numerous cytokines have been molecularly characterized. Analysis of their amino acid sequences shows that some of these receptors bear certain motifs in their extracellular domains that define a family of receptors called the Hematopoietin receptor superfamily. Significant advances in characterizing the structure, function, and mechanisms of signal transduction have been made for several members of this family. The purpose of this review is to discuss the recent advances made for one of the family members, the interleukin (IL) 4 receptor. Other receptor systems have recently been reviewed elsewhere. The IL-4 receptor consists of, at the minimum, the cloned 140 kDa IL-4-binding chain with the potential for associating with other chains. The IL-4 receptor transduces its signal by activating a tyrosine kinase that phosphorylates cellular substrates, including the receptor itself, and the 170 kDa substrate called 4PS. Phosphorylated 4PS interacts with the SH2 domain of the enzyme PI-3'-kinase and increases its enzymatic activity. These early events in the IL-4 receptor initiated signaling pathway may trigger a series of signals that will ultimately lead to an IL-4 specific biologic outcome.

  15. A speedup technique for (l, d-motif finding algorithms

    Directory of Open Access Journals (Sweden)

    Dinh Hieu

    2011-03-01

    Full Text Available Abstract Background The discovery of patterns in DNA, RNA, and protein sequences has led to the solution of many vital biological problems. For instance, the identification of patterns in nucleic acid sequences has resulted in the determination of open reading frames, identification of promoter elements of genes, identification of intron/exon splicing sites, identification of SH RNAs, location of RNA degradation signals, identification of alternative splicing sites, etc. In protein sequences, patterns have proven to be extremely helpful in domain identification, location of protease cleavage sites, identification of signal peptides, protein interactions, determination of protein degradation elements, identification of protein trafficking elements, etc. Motifs are important patterns that are helpful in finding transcriptional regulatory elements, transcription factor binding sites, functional genomics, drug design, etc. As a result, numerous papers have been written to solve the motif search problem. Results Three versions of the motif search problem have been proposed in the literature: Simple Motif Search (SMS, (l, d-motif search (or Planted Motif Search (PMS, and Edit-distance-based Motif Search (EMS. In this paper we focus on PMS. Two kinds of algorithms can be found in the literature for solving the PMS problem: exact and approximate. An exact algorithm identifies the motifs always and an approximate algorithm may fail to identify some or all of the motifs. The exact version of PMS problem has been shown to be NP-hard. Exact algorithms proposed in the literature for PMS take time that is exponential in some of the underlying parameters. In this paper we propose a generic technique that can be used to speedup PMS algorithms. Conclusions We present a speedup technique that can be used on any PMS algorithm. We have tested our speedup technique on a number of algorithms. These experimental results show that our speedup technique is indeed very

  16. Evaluating deterministic motif significance measures in protein databases

    Directory of Open Access Journals (Sweden)

    Azevedo Paulo J

    2007-12-01

    Full Text Available Abstract Background Assessing the outcome of motif mining algorithms is an essential task, as the number of reported motifs can be very large. Significance measures play a central role in automatically ranking those motifs, and therefore alleviating the analysis work. Spotting the most interesting and relevant motifs is then dependent on the choice of the right measures. The combined use of several measures may provide more robust results. However caution has to be taken in order to avoid spurious evaluations. Results From the set of conducted experiments, it was verified that several of the selected significance measures show a very similar behavior in a wide range of situations therefore providing redundant information. Some measures have proved to be more appropriate to rank highly conserved motifs, while others are more appropriate for weakly conserved ones. Support appears as a very important feature to be considered for correct motif ranking. We observed that not all the measures are suitable for situations with poorly balanced class information, like for instance, when positive data is significantly less than negative data. Finally, a visualization scheme was proposed that, when several measures are applied, enables an easy identification of high scoring motifs. Conclusion In this work we have surveyed and categorized 14 significance measures for pattern evaluation. Their ability to rank three types of deterministic motifs was evaluated. Measures were applied in different testing conditions, where relations were identified. This study provides some pertinent insights on the choice of the right set of significance measures for the evaluation of deterministic motifs extracted from protein databases.

  17. Benefits of X-Ray CMT for the modeling of C/C composites

    Energy Technology Data Exchange (ETDEWEB)

    Coindreau, Olivia; Lachaud, Jean; Vignoles, Gerard L. [LCTS - UMR 5801 CNRS-Universite Bordeaux 1-Safran-CEA 3, Allee La Boetie, Pessac, F33600 (France); Mulat, Christianne [LCTS - UMR 5801 CNRS-Universite Bordeaux 1-Safran-CEA 3, Allee La Boetie, Pessac, F33600 (France); IMS - UMR5218 CNRS-Universite Bordeaux 1-IPB 351, Avenue de la Liberation, Talence, F33410 (France); Germain, Christian [IMS - UMR5218 CNRS-Universite Bordeaux 1-IPB 351, Avenue de la Liberation, Talence, F33410 (France)

    2011-03-15

    C/C composites have application in very demanding areas like aerospace, fusion technology, etc. and thus their optimization is crucial, both in the control of processing routes and in the prediction of their behavior in use. Intense modeling efforts have been performed in these directions. To help a direct application on actual materials, with possibly complex reinforcement architectures, X-ray computerized micro-tomography (CMT) is a beneficial technique, since it allows producing extremely detailed representations of these architectures. However, there is a long way from the crude X-ray projections to the information that is directly usable in C/C composite modeling. This paper summarizes several achievements in this domain and discusses the obtained results, concerning (i) composites imaging by phase contrast CMT and holographic CMT, (ii) evaluation of effective geometrical and transfer properties in fiber arrangements and actual fiber-reinforced composites, (iii) modeling of degradation by ablation, and (iv) modeling of processing by chemical vapor infiltration. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  18. A Novel Method for Preparation of TaC Coating on C/C Composite Material

    Institute of Scientific and Technical Information of China (English)

    Hanwei HE; Kechao ZHOU; Xiang XIONG

    2005-01-01

    A new method for preparation of TaC coating on C/C composite material is reported. The amorphous ethylate tantalum jellied as the precursor is prepared and spread densely on the surface of the C/C composite material so as to form a multilayer film. In a graphitization furnace the multilayer film is transformed into TaC coating at various temperatures. Ethylate tantalum film is characterized by FT-IR (Fourier transform infrared) spectra, XRD (X-ray diffraction) and SEM (scanning electron microscopy) and TaC coating is characterized by XRD and SEM. At 1200℃the coating contained TaC and Ta2O5, and at above 1400℃ only TaC is formed. The coating formed at 1600℃ is a continuous stratum structure, and that formed at 1600℃ is a porous net structure. Analysis on thermodynamics and formation mechanism of TaC indicates that, after ethylate tantalum is decomposed, Ta2O5 is first produced and then transformed into Ta2C, and newly formed Ta2C is transformed into TaC by the sufficient C at last.

  19. Identification of protein superfamily from structure- based sequence motif

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The structure-based sequence motif of the distant proteins in evolution, protein tyrosine phosphatases (PTP) Ⅰ and Ⅱ superfamilies, as an example, has been defined by the structural comparison, structure-based sequence alignment and analyses on substitution patterns of residues in common sequence conserved regions. And the phosphatases Ⅰ and Ⅱ can be correctly identified together by the structure-based PTP sequence motif from SWISS-PROT and TrEBML databases. The results show that the correct rates of identification are over 98%. This is the first time to identify PTP Ⅰ and Ⅱ together by this motif.

  20. A comprehensive search for recombinogenic motifs in the human genome.

    Directory of Open Access Journals (Sweden)

    Henry R Johnston

    Full Text Available The patterns of male and female recombination vary greatly on a macro scale. A unique motif in each gender, triggering a double strand break at its location, much in the way Chi sites operate in E. coli, could logically explain this difference. As such, we have undertaken a comprehensive search of all small motifs in an attempt to identify one or more that match to the available data. In the end, we conclude that no such motifs appear to exist in the human genome.

  1. Would be the photon a composed particle? / Sobre a possibilidade da quantiza\\c{c}\\~ao dos fluxos de campo na radia\\c{c}\\~ao eletromagn\\'etica

    CERN Document Server

    Duarte, Celso de Araujo

    2013-01-01

    Here it is made a comparative analysis between the classical and the quantum expressions for the energy of electromagnetic radiation (ER). The comparison points to the possibility of the quantization of the magnetic and the electric field fluxes in the ER. ----- Apresenta-se uma an\\'alise comparativa entre as express\\~oes cl\\'assica e qu\\^antica para a energia da radia\\c{c}\\~ao eletromagn\\'etica (RE). A compara\\c{c}\\~ao nos aponta para a possibilidade de haver uma quantiza\\c{c}\\~ao dos fluxos dos campos magn\\'etico e el\\'etrico na RE.

  2. A Novel Alignment-Free Method for Comparing Transcription Factor Binding Site Motifs

    OpenAIRE

    Minli Xu; Zhengchang Su

    2010-01-01

    BACKGROUND: Transcription factor binding site (TFBS) motifs can be accurately represented by position frequency matrices (PFM) or other equivalent forms. We often need to compare TFBS motifs using their PFMs in order to search for similar motifs in a motif database, or cluster motifs according to their binding preference. The majority of current methods for motif comparison involve a similarity metric for column-to-column comparison and a method to find the optimal position alignment between ...

  3. ROMANIAN FOLKLORE MOTIFS IN FASHION DESIGN

    Directory of Open Access Journals (Sweden)

    MOCENCO Alexandra

    2014-05-01

    Full Text Available The traditional Romanian costume such as the entire popular art (architecture, woodcarvins, pottery etc. was born and lasted in our country since ancient times. Closely related to human existence, the traditional costume reflected over the years as reflected nowadays, the mentality and artistic conception of the people. Today the traditional Romanian costume became an inspiration source to the wholesale fashion production industry designers, both Romanian and international. Although the contemporary designers are working in accordance with a vision, using a wide area of styles, methods and current technology, they usually return to traditional techniques and ethnic folklore motifs, which converts and resize them, integrating them in their contemporary space. Adrian Oianu is a very appreciated Romanian designer who launched two collections inspired by his native’s country traditional costumes: “Suflecata pan’ la brau” (“Turned up ‘til the belt” and “Bucurie” (“Joy”. Dorin Negrau had as inspiration for his “Lost” collection the traditional costume from the Bihor region. Yves Saint Laurent had a collection inspired by the Romanian traditional flax blouses called “La blouse roumaine”. The paper presents the traditional Romanian values throw fashion collections. The research activity will create innovative concepts to support the garment industry in order to develop their own brand and to bring the design activities in Romania at an international level. The research was conducted during the initial stage of a project, financed through national founds, consisting in a documentary study on ethnographic characteristics of the popular costume from different regions of the country.

  4. Targeting functional motifs of a protein family

    Science.gov (United States)

    Bhadola, Pradeep; Deo, Nivedita

    2016-10-01

    The structural organization of a protein family is investigated by devising a method based on the random matrix theory (RMT), which uses the physiochemical properties of the amino acid with multiple sequence alignment. A graphical method to represent protein sequences using physiochemical properties is devised that gives a fast, easy, and informative way of comparing the evolutionary distances between protein sequences. A correlation matrix associated with each property is calculated, where the noise reduction and information filtering is done using RMT involving an ensemble of Wishart matrices. The analysis of the eigenvalue statistics of the correlation matrix for the β -lactamase family shows the universal features as observed in the Gaussian orthogonal ensemble (GOE). The property-based approach captures the short- as well as the long-range correlation (approximately following GOE) between the eigenvalues, whereas the previous approach (treating amino acids as characters) gives the usual short-range correlations, while the long-range correlations are the same as that of an uncorrelated series. The distribution of the eigenvector components for the eigenvalues outside the bulk (RMT bound) deviates significantly from RMT observations and contains important information about the system. The information content of each eigenvector of the correlation matrix is quantified by introducing an entropic estimate, which shows that for the β -lactamase family the smallest eigenvectors (low eigenmodes) are highly localized as well as informative. These small eigenvectors when processed gives clusters involving positions that have well-defined biological and structural importance matching with experiments. The approach is crucial for the recognition of structural motifs as shown in β -lactamase (and other families) and selectively identifies the important positions for targets to deactivate (activate) the enzymatic actions.

  5. Early illness recognition using frequent motif discovery.

    Science.gov (United States)

    Hajihashemi, Zahra; Popescu, Mihail

    2015-08-01

    Living alone in their own residence, older adults are at risk for late assessment of physical or cognitive changes due to many factors such as their impression that such changes are simply a normal part of aging or their reluctance to admit to a problem. This paper describes an early illness recognition framework using sensor network technology to identify the health trajectory of older adults reflected in patterns of day-today activities. Describing the behavior of older adults could help clinicians to identify those at the greatest risk for functional decline and adverse events. The proposed framework, denoted as Abnormal Frequent Activity Pattern (AFAP), is based on the identification of known past abnormal frequent activities in current sensor data. More specifically, AFAP declares a day abnormal when past frequent abnormal behavior patterns, not found during normal days, are discovered in the current activity data. While AFAP requires the labeling of past days as normal/abnormal, it doesn't need specific activity identification. Frequent activity patterns (FAP) are found using MEME, a bioinformatics motif detection algorithm. To validate our approach, we used data obtained from TigerPlace, an aging in place community situated in Columbia, MO, where apartments are equipped with sensor networks (motion, bed and depth sensors). A retrospective multiple case study (N=3) design was used to quantify the in-home older adult's daily routines, over a period of two weeks. Within-person variability of routine activities may be used as a new predictor in the study of health trajectories of older adults. PMID:26737096

  6. An autoinhibited conformation of LGN reveals a distinct interaction mode between GoLoco motifs and TPR motifs.

    Science.gov (United States)

    Pan, Zhu; Zhu, Jinwei; Shang, Yuan; Wei, Zhiyi; Jia, Min; Xia, Caihao; Wen, Wenyu; Wang, Wenning; Zhang, Mingjie

    2013-06-01

    LGN plays essential roles in asymmetric cell divisions via its N-terminal TPR-motif-mediated binding to mInsc and NuMA. This scaffolding activity requires the release of the autoinhibited conformation of LGN by binding of Gα(i) to its C-terminal GoLoco (GL) motifs. The interaction between the GL and TPR motifs of LGN represents a distinct GL/target binding mode with an unknown mechanism. Here, we show that two consecutive GL motifs of LGN form a minimal TPR-motif-binding unit. GL12 and GL34 bind to TPR0-3 and TPR4-7, respectively. The crystal structure of a truncated LGN reveals that GL34 forms a pair of parallel α helices and binds to the concave surface of TPR4-7, thereby preventing LGN from binding to other targets. Importantly, the GLs bind to TPR motifs with a mode distinct from that observed in the GL/Gα(i)·GDP complexes. Our results also indicate that multiple and orphan GL motif proteins likely respond to G proteins with distinct mechanisms.

  7. G Protein–Coupled Receptor Rhodopsin

    OpenAIRE

    Palczewski, Krzysztof

    2006-01-01

    The rhodopsin crystal structure provides a structural basis for understanding the function of this and other G protein–coupled receptors (GPCRs). The major structural motifs observed for rhodopsin are expected to carry over to other GPCRs, and the mechanism of transformation of the receptor from inactive to active forms is thus likely conserved. Moreover, the high expression level of rhodopsin in the retina, its specific localization in the internal disks of the photoreceptor structures [term...

  8. Local graph alignment and motif search in biological networks

    Science.gov (United States)

    Berg, Johannes; Lässig, Michael

    2004-10-01

    Interaction networks are of central importance in postgenomic molecular biology, with increasing amounts of data becoming available by high-throughput methods. Examples are gene regulatory networks or protein interaction maps. The main challenge in the analysis of these data is to read off biological functions from the topology of the network. Topological motifs, i.e., patterns occurring repeatedly at different positions in the network, have recently been identified as basic modules of molecular information processing. In this article, we discuss motifs derived from families of mutually similar but not necessarily identical patterns. We establish a statistical model for the occurrence of such motifs, from which we derive a scoring function for their statistical significance. Based on this scoring function, we develop a search algorithm for topological motifs called graph alignment, a procedure with some analogies to sequence alignment. The algorithm is applied to the gene regulation network of Escherichia coli.

  9. Review article: The mountain motif in the plot of Matthew

    Directory of Open Access Journals (Sweden)

    Gert J. Volschenk

    2010-02-01

    Full Text Available This article reviewed T.L. Donaldson’s book, Jesus on the mountain: A study in Matthean theology, published in 1985 by JSOT Press, Sheffield, and focused on the mountain motif in the structure and plot of the Gospel of Matthew, in addition to the work of Donaldson on the mountain motif as a literary motif and as theological symbol. The mountain is a primary theological setting for Jesus’ ministry and thus is an important setting, serving as one of the literary devices by which Matthew structured and progressed his narrative. The Zion theological and eschatological significance and Second Temple Judaism serve as the historical and theological background for the mountain motif. The last mountain setting (Mt 28:16–20 is the culmination of the three theological themes in the plot of Matthew, namely Christology, ecclesiology and salvation history.

  10. Closing the gap between MC3 and MC5 metallacumulenes: the chemistry of the first structurally characterized transition-metal complex with M=C=C=C=CR2 as the molecular unit.

    Science.gov (United States)

    Ilg, Kerstin; Werner, Helmut

    2002-06-17

    The reactions of the dihydrido compound [IrH2Cl(PiPr3)2] (3) with HC identical to CC(O)CHPh2 and HC identical to CC(OAc)=CPh2 lead to the formation of alkynyl-(hydrido)iridium(III) and vinylideneiridium(I) complexes 4-7 which, however, are not suitable precursors for the target molecule trans-[IrCl(=C=C=C=CPh2)-(PiPr3)2] (8). Compound 8 has been prepared in 77% yield from 3 and the vinyl triflate HC identical to CC(OTf)=CPh2 in the presence of NEt3. Treatment of 8 with CF3CO2H affords the vinylvinylidene complex trans-[IrCl(=C=CHC(O2C-CF3)=CPh2)(PiPr3)2] (10) by addition of the electrophile to the C beta-C gamma bond of the MC4 chain. In contrast, the reaction of 8 with HCl yields the five-coordinate butadienyliridium(III) compound [IrCl2-(eta 1-(Z)-CH=CHC(Cl)=CPh2)(PiPr3)2] (11). Salt metathesis of 8 with KI, KOH, and NaN3 leads to the formation of the substitution products trans-[IrX-(=C=C=C=CPh2)(PiPr3)2] (12-14) of which the hydroxo derivative 13 reacts with phenol to give trans-[Ir(OPh)(=C=C=C=CPh2)(PiPr3)2] (15). From 13 and methanol, the octahedral dihydridoiridium(III) complex [IrH2(CH=C=C=CPh2)(CO)(PiPr3)2] (16) is formed by fragmentation of the alcohol. In the presence of CO, both the methyl compound trans-[Ir(CH3)(=C=C=C=CPh2)-(PiPr3)2] (17) (generated from 8 and CH3Li) and the azido complex 14 (X=N3) undergo migratory insertion reactions to yield the four-coordinate iridium(I) carbonyls trans-[Ir(C(C identical to CCH3)=CPh2)(CO)(PiPr3)2] (18) and trans-[Ir(C identical to CC(N3)=CPh2)(CO)(PiPr3)2] (19), respectively. Compound 19 rearranges slowly to the thermodynamically more stable isomer trans-[Ir(C(N3)=C=C=CPh2)(CO)(PiPr3)2] (20). The molecular structures of 8 and 18 have been determined crystallographically. PMID:12391660

  11. NCBI nr-aa BLAST: CBRC-OPRI-01-0259 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OPRI-01-0259 ref|NP_001129442.1| chemokine (C-C motif) receptor 3 [Felis catus...] gb|ACI42420.1| chemokine (C-C motif) receptor 3 [Felis catus] gb|ACJ13514.1| CC chemokine receptor 3 [Felis catus] NP_001129442.1 1e-140 71% ...

  12. NCBI nr-aa BLAST: CBRC-MLUC-01-0017 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MLUC-01-0017 ref|NP_001129441.1| chemokine (C-C motif) receptor 1 [Felis catus...] gb|ACI42419.1| chemokine (C-C motif) receptor 1 [Felis catus] gb|ACJ13513.1| CC chemokine receptor 1 [Felis catus] NP_001129441.1 1e-118 78% ...

  13. NCBI nr-aa BLAST: CBRC-VPAC-01-0317 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-VPAC-01-0317 ref|NP_001129441.1| chemokine (C-C motif) receptor 1 [Felis catus...] gb|ACI42419.1| chemokine (C-C motif) receptor 1 [Felis catus] gb|ACJ13513.1| CC chemokine receptor 1 [Felis catus] NP_001129441.1 1e-148 78% ...

  14. NCBI nr-aa BLAST: CBRC-VPAC-01-1032 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-VPAC-01-1032 ref|NP_001129442.1| chemokine (C-C motif) receptor 3 [Felis catus...] gb|ACI42420.1| chemokine (C-C motif) receptor 3 [Felis catus] gb|ACJ13514.1| CC chemokine receptor 3 [Felis catus] NP_001129442.1 5e-32 52% ...

  15. NCBI nr-aa BLAST: CBRC-MEUG-01-2041 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MEUG-01-2041 ref|NP_001129442.1| chemokine (C-C motif) receptor 3 [Felis catus...] gb|ACI42420.1| chemokine (C-C motif) receptor 3 [Felis catus] gb|ACJ13514.1| CC chemokine receptor 3 [Felis catus] NP_001129442.1 1e-144 70% ...

  16. Robust and Adaptive MicroRNA-Mediated Incoherent Feedforward Motifs

    Science.gov (United States)

    Xu, Feng-Dan; Liu, Zeng-Rong; Zhang, Zhi-Yong; Shen, Jian-Wei

    2009-02-01

    We integrate transcriptional and post-transcriptional regulation into microRNA-mediated incoherent feedforward motifs and analyse their dynamical behaviour and functions. The analysis show that the behaviour of the system is almost uninfluenced by the varying input in certain ranges and by introducing of delay and noise. The results indicate that microRNA-mediated incoherent feedforward motifs greatly enhance the robustness of gene regulation.

  17. Robust and Adaptive MicroRNA-Mediated Incoherent Feedforward Motifs

    Institute of Scientific and Technical Information of China (English)

    XU Feng-Dan; LIU Zeng-Rong; ZHANG Zhi-Yong; SHEN Jian-Wei

    2009-01-01

    We integrate transcriptional and post-transcriptional regulation into microRNA-mediated incoherent feedforward motifs and analyse their dynamical behaviour and functions. The analysis show that the behaviour of the system is almost uninfluenced by the varying input in certain ranges and by introducing of delay and noise. The results indicate that microRNA-mediated incoherent feedforward motifs greatly enhance the robustness of gene regulation.

  18. Mining Tertiary Structural Motifs for Assessment of Designability

    OpenAIRE

    Zhang, Jian; Grigoryan, Gevorg

    2013-01-01

    The observation of a limited secondary-structural alphabet in native proteins, with significant sequence preferences, has profoundly influenced the fields of protein design and structure prediction (Simons et al., 1997; Verschueren et al., 2011). In the era of structural genomics, as the size of the structural dataset continues to grow rapidly, it is becoming possible to extend this analysis to tertiary structural motifs and their sequences. For a hypothetical tertiary motif, the rate of its ...

  19. Temporal Analysis of Motif Mixtures using Dirichlet Processes

    OpenAIRE

    Emonet, Rémi; Varadarajan, J.; Odobez, Jean-Marc

    2014-01-01

    International audience In this paper, we present a new model for unsupervised discovery of recurrent temporal patterns (or motifs) in time series (or documents). The model is designed to handle the difficult case of multivariate time series obtained from a mixture of activities, that is, our observations are caused by the superposition of multiple phenomena occurring concurrently and with no synchronization. The model uses nonparametric Bayesian methods to describe both the motifs and thei...

  20. Triplex-induced recombination and repair in the pyrimidine motif

    OpenAIRE

    Kalish, Jennifer M.; Seidman, Michael M.; Weeks, Daniel L.; Glazer, Peter M.

    2005-01-01

    Triplex-forming oligonucleotides (TFOs) bind DNA in a sequence-specific manner at polypurine/polypyrimidine sites and mediate targeted genome modification. Triplexes are formed by either pyrimidine TFOs, which bind parallel to the purine strand of the duplex (pyrimidine, parallel motif), or purine TFOs, which bind in an anti-parallel orientation (purine, anti-parallel motif). Both purine and pyrimidine TFOs, when linked to psoralen, have been shown to direct psoralen adduct formation in cells...

  1. Cross-Disciplinary Detection and Analysis of Network Motifs

    OpenAIRE

    Ngoc Tam L. Tran; Luke DeLuccia; McDonald, Aidan F; Chun-Hsi Huang

    2015-01-01

    The detection of network motifs has recently become an important part of network analysis across all disciplines. In this work, we detected and analyzed network motifs from undirected and directed networks of several different disciplines, including biological network, social network, ecological network, as well as other networks such as airlines, power grid, and co-purchase of political books networks. Our analysis revealed that undirected networks are similar at the basic three and four nod...

  2. The Origin of Motif Families in Food Webs

    OpenAIRE

    Klaise, Janis; Johnson, Samuel

    2016-01-01

    Food webs have been found to exhibit remarkable motif profiles, patterns in the relative prevalences of all possible three-species sub-graphs, and this has been related to ecosystem properties such as stability and robustness. Analysing 46 food webs of various kinds, we find that most food webs fall into one of two distinct motif families. The separation between the families is well predicted by a global measure of hierarchical order in directed networks - trophic coherence. We find that trop...

  3. Motif depletion in bacteriophages infecting hosts with CRISPR systems

    OpenAIRE

    Kupczok, Anne; Bollback, Jonathan P

    2014-01-01

    Background CRISPR is a microbial immune system likely to be involved in host-parasite coevolution. It functions using target sequences encoded by the bacterial genome, which interfere with invading nucleic acids using a homology-dependent system. The system also requires protospacer associated motifs (PAMs), short motifs close to the target sequence that are required for interference in CRISPR types I and II. Here, we investigate whether PAMs are depleted in phage genomes due to selection pre...

  4. Comparative Study of R.C.C and Steel Concrete Composite Structures

    Directory of Open Access Journals (Sweden)

    Shweta A. Wagh

    2014-04-01

    Full Text Available Steel concrete composite construction has gained wide acceptance world wide as an alternative to pure steel and pure concrete construction. The use of steel in construction industry is very low in India compared to many developing countries. There is a great potential for increasing the volume of steel in construction, especially in the current development needs India and not using steel as an alternative construction material and not using it where it is economical is a heavy loss for the country. In this paper study of Four various multistoried commercial buildings i.e. G+12, G+16, G+20, G+24 are analysed by using STAAD-Pro software. Where design and cost estimation is carried out using MS-Excel programming and from obtained result comparison can be made between R.C.C and composite structure.

  5. Sintering Behaviour of Al2O3-SiC-C Ramming Mix

    Institute of Scientific and Technical Information of China (English)

    WUXingrong; CAOFeng

    2004-01-01

    Silicon fines, boron acid solid powders and microfine SiO2 as sintering agents were incorporated into Al2O3-SiC-C ramming mix in order to investigated their effects on the microstructure , mechanical properties and sintering behavior of the ramming mix. Results show that all the three agents could improved both densification and mehanical properties markedly, compared to that of non-agent specimens and the effect of the composite of boron acid solid powders and microfine SiO2 is the best. The oxidation resistance increased with the addition of agents, which is supported by densification. Microstructures showed that agent powders could fill pores or produce liquid phases at high temperature, therefore, improve the sintering of the ramming mix.

  6. Architectural Visualization of C/C++ Source Code for Program Comprehension

    Energy Technology Data Exchange (ETDEWEB)

    Panas, T; Epperly, T W; Quinlan, D; Saebjornsen, A; Vuduc, R

    2006-09-01

    Structural and behavioral visualization of large-scale legacy systems to aid program comprehension is still a major challenge. The challenge is even greater when applications are implemented in flexible and expressive languages such as C and C++. In this paper, we consider visualization of static and dynamic aspects of large-scale scientific C/C++ applications. For our investigation, we reuse and integrate specialized analysis and visualization tools. Furthermore, we present a novel layout algorithm that permits a compressive architectural view of a large-scale software system. Our layout is unique in that it allows traditional program visualizations, i.e., graph structures, to be seen in relation to the application's file structure.

  7. Iron-Catalyzed C-C Cross-Couplings Using Organometallics.

    Science.gov (United States)

    Guérinot, Amandine; Cossy, Janine

    2016-08-01

    Over the last decades, iron-catalyzed cross-couplings have emerged as an important tool for the formation of C-C bonds. A wide variety of alkenyl, aryl, and alkyl (pseudo)halides have been coupled to organometallic reagents, the most currently used being Grignard reagents. Particular attention has been devoted to the development of iron catalysts for the functionalization of alkyl halides that are generally challenging substrates in classical cross-couplings. The high functional group tolerance of iron-catalyzed cross-couplings has encouraged organic chemists to use them in the synthesis of bioactive compounds. Even if some points remain obscure, numerous studies have been carried out to investigate the mechanism of iron-catalyzed cross-coupling and several hypotheses have been proposed. PMID:27573401

  8. Mesophase formation of coal-tar pitches used for impregnant of C/C composites

    Institute of Scientific and Technical Information of China (English)

    巩前明; 黄启忠; 黄伯云; 张福勤; 陈腾飞

    2001-01-01

    By a polarized light optical microscopy with a hot stage, liquid-phase nuclear magnetic resonance 13 C-NMR and 1 H-NMR, X-ray diffractometry and scanning electron microscopy (SEM), the factors that affect the formation of mesophase in C/C composites, such as pressure, quinoline insolubles (QI) and heterocylic compounds, were analyzed. Further, the graphitizability of the resultant carbon was discussed. The results indicate that to some degree, QI contents accelerate the formation of mesophase at atmospheric pressure; while at high pressure, the coalescence and growth of mesophase spherules are impeded and the resultant coke produced from higher QI content pitch is harder to be graphitized. This is in agreement with the transfer of microstructure from domain anisotropy to fine-grained mosaics.

  9. Sintering Behaviour of Al2O3-SiC-C Ramming Mix

    Institute of Scientific and Technical Information of China (English)

    WU Xingrong; CAO Feng

    2004-01-01

    Silicon fines, boron acid solid powders and microfine SiO2 as sintering agents were incorporated into Al2O3-SiC-C ramming mix in order to investigated their effects on the microstructue,mechanical properties and sintering be-havior of the ramming mix.Results show that all the three agents could improved both densification and mehanical properties markedly,compared to that of non-agent speci-mens and the effect of the composite of boron acid solid powders and microfine SiO2 is the best.The oxidation re-sistance increased with the addition of agents,which is supported by densification.Microstructures shoued that a-gent powders could fill pores or produce liquid phases at high temperatuer,therefore,improve the sintering of the ramming mix.

  10. Microstructure characteristic and formation mechanism of crackfree TaC coating on C/C composite

    Institute of Scientific and Technical Information of China (English)

    LI Guo-dong; XIONG Xiang; HUANG Bai-yun

    2005-01-01

    The microstructure characteristic and formation mechanism of the crackfree and ablation-resistant TaC coating deposited on the C/C composite by Chemical Vapour Deposition(CVD) were investigated, using the reaction system of TaCl5-C3H6-H2-Ar. The results show that the nanosized pore structure formed in the TaC coating interior during CVD process is the main factor to reduce the hardness, elastic modulus, linear expansibility and inner thermal stress. Then crackfree coatings can be prepared and their thermal shock resistance can be enhanced. To obtain the dense and homogeneous matrix surface is necessary for the crackfree and low stress coating. The TaC coating structure that distributes from the dense matrix towards loose coating surface will result in the thick crackfree coating with good thermal shock resistance.

  11. In silico analysis of molecular mechanisms of Galanthus nivalis agglutinin-related lectin-induced cancer cell death from carbohydrate-binding motif evolution hypothesis.

    Science.gov (United States)

    Yu, Qi-Jia; Li, Zi-Yue; Yao, Shun; Ming, Miao; Wang, Shu-Ya; Liu, Bo; Bao, Jin-Ku

    2011-10-01

    Galanthus nivalis agglutinin-related lectins, a superfamily of strictly mannose-binding-specific lectins widespread amongst monotyledonous plants, have drawn a rising attention for their remarkable anti-proliferative and apoptosis-inducing activities toward various types of cancer cells; however, the precise molecular mechanisms by which they induce tumor cell apoptosis are still only rudimentarily understood. Herein, we found that the three conserved motifs "QXDXNXVXY," the mannose-specific binding sites, could mutate at one or more amino acid sites, which might be a driving force for the sequential evolution and thus ultimately leading to the complete disappearance of the three conserved motifs. In addition, we found that the motif evolution could result in the diversification of sugar-binding types that G. nivalis agglutinin-related lectins could bind from specific mannose receptors to more types of sugar-containing receptors in cancer cells. Subsequently, we indicated that some sugar-containing receptors such as TNFR1, EGFR, Hsp90, and Hsp70 could block downstream anti-apoptotic or survival signaling pathways, which, in turn, resulted in tumor cell apoptosis. Taken together, our hypothesis that carbohydrate-binding motif evolution may impact the G. nivalis agglutinin-related lectin-induced survival or anti-apoptotic pathways would provide a new perspective for further elucidating the intricate relationships between the carbohydrate-binding specificities and complex molecular mechanisms by which G. nivalis agglutinin-related lectins induce cancer cell death.

  12. Overview of C/C-SiC Composite Development for the Orion Launch Abort System

    Science.gov (United States)

    Allen, Lee R.; Valentine, Peter G.; Schofield, Elizabeth S.; Beshears, Ronald D.; Coston, James E.

    2012-01-01

    Past and present efforts by the authors to further understanding of the ceramic matrix composite (CMC) material used in the valve components of the Orion Launch Abort System (LAS) Attitude Control Motor (ACM) will be presented. The LAS is designed to quickly lift the Orion Crew Exploration Vehicle (CEV) away from its launch vehicle in emergency abort scenarios. The ACM is a solid rocket motor which utilizes eight throttleable nozzles to maintain proper orientation of the CEV during abort operations. Launch abort systems have not been available for use by NASA on manned launches since the last Apollo ]Saturn launch in 1975. The CMC material, carbon-carbon/silicon-carbide (C/C-SiC), is manufactured by Fiber Materials, Inc. and consists of a rigid 4-directional carbon-fiber tow weave reinforced with a mixed carbon plus SiC matrix. Several valve and full system (8-valve) static motor tests have been conducted by the motor vendor. The culmination of these tests was the successful flight test of the Orion LAS Pad Abort One (PA ]1) vehicle on May 6, 2010. Due to the fast pace of the LAS development program, NASA Marshall Space Flight Center assisted the LAS community by performing a series of material and component evaluations using fired hardware from valve and full ]system development motor tests, and from the PA-1 flight ACM motor. Information will be presented on the structure of the C/C-SiC material, as well as the efficacy of various non ]destructive evaluation (NDE) techniques, including but not limited to: radiography, computed tomography, nanofocus computed tomography, and X-ray transmission microscopy. Examinations of the microstructure of the material via scanning electron microscopy and energy dispersive spectroscopy will also be discussed. The findings resulting from the subject effort are assisting the LAS Project in risk assessments and in possible modifications to the final ACM operational design.

  13. C,C'-bis(benzodiazaborolyl)dicarba-closo-dodecaboranes: synthesis, structures, photophysics and electrochemistry.

    Science.gov (United States)

    Weber, Lothar; Kahlert, Jan; Brockhinke, Regina; Böhling, Lena; Halama, Johannes; Brockhinke, Andreas; Stammler, Hans-Georg; Neumann, Beate; Nervi, Carlo; Harder, Rachel A; Fox, Mark A

    2013-08-14

    Six new C,C'-bis(benzodiazaborolyl)dicarba-closo-dodecaboranes, 1,A-R2-1,A-C2B10H10, where R represents the group 2-(1,3-Et2-1,3,2-N2BC6H4) or 2-(1,3-Ph2-1,3,2-N2BC6H4) and A is 2, 7 or 12, were synthesized from o-, m-, and p-dicarbadodecaboranes (carboranes) by lithiation and subsequent treatment with the respective 2-bromo-1,3,2-benzodiazaboroles. UV-visible and fluorescence spectra of all carboranes display low energy charge transfer emissions. While such emissions with Stokes shifts between 17,330 and 21,290 cm(-1) are typical for C,C'-bis(aryl)-ortho-carboranes, the observed low-energy emissions with Stokes shifts between 8320 and 15,170 cm(-1) for the meta- and para-isomers are unusual as high-energy emissions are typical for meta- and para-dicarbadodecaboranes. Fluorescence quantum yields (φF) for the novel 1,7- and 1,12-bis(benzodiazaborolyl)-carboranes depend on the substituents at the nitrogen atoms of the heterocycle. Thus, the para-carborane with N-ethyl substituents 1,12-(1',3'-Et2-1',3',2'-N2BC6H4)2-1,12-C2B10H10 has a φF value of 41% in cyclohexane solution and only of 9% in the solid state, whereas the analogous 1,12-(1',3'-Ph2-1',3',2'-N2BC6H4)2-1,12-C2B10H10 shows quantum yields of 3% in cyclohexane solution and 72% in the solid state. X-ray crystallographic, computational and cyclic voltammetry studies for these carboranes are also presented.

  14. Transcriptional Network growing Models using Motif-based Preferential Attachment

    Directory of Open Access Journals (Sweden)

    Ahmed Farouk Abdelzaher

    2015-10-01

    Full Text Available Understanding relationships between architectural properties of gene-regulatory networks (GRNs has been one of the major goals in systems biology and bioinformatics, as it can provide insights into, e.g., disease dynamics and drug development. Such GRNs are characterized by their scale-free degree distributions and existence of network motifs--i.e., small-node subgraphs that occur more abundantly in GRNs than expected from chance alone. Because these transcriptional modules represent ``building blocks'' of complex networks and exhibit a wide range of functional and dynamical properties, they may contribute to the remarkable robustness and dynamical stability associated with the whole of GRNs. Here we developed network-construction models to better understand this relationship, which produce randomized GRNs by using transcriptional motifs as the fundamental growth unit in contrast to other methods that construct similar networks on a node-by-node basis. Because this model produces networks with a prescribed lower bound on the number of choice transcriptional motifs (e.g., downlinks, feed-forward loops, its fidelity to the motif distributions observed in model organisms represents an improvement over existing methods, which we validated by contrasting their resultant motif and degree distributions against existing network-growth models and data from the model organism of the bacterium Escherichia coli. These models may therefore serve as novel testbeds for further elucidating relationships between the topology of transcriptional motifs and network-wide dynamical properties.

  15. Discovering Motifs in Biological Sequences Using the Micron Automata Processor.

    Science.gov (United States)

    Roy, Indranil; Aluru, Srinivas

    2016-01-01

    Finding approximately conserved sequences, called motifs, across multiple DNA or protein sequences is an important problem in computational biology. In this paper, we consider the (l, d) motif search problem of identifying one or more motifs of length l present in at least q of the n given sequences, with each occurrence differing from the motif in at most d substitutions. The problem is known to be NP-complete, and the largest solved instance reported to date is (26,11). We propose a novel algorithm for the (l,d) motif search problem using streaming execution over a large set of non-deterministic finite automata (NFA). This solution is designed to take advantage of the micron automata processor, a new technology close to deployment that can simultaneously execute multiple NFA in parallel. We demonstrate the capability for solving much larger instances of the (l, d) motif search problem using the resources available within a single automata processor board, by estimating run-times for problem instances (39,18) and (40,17). The paper serves as a useful guide to solving problems using this new accelerator technology. PMID:26886735

  16. An experimental test of a fundamental food web motif.

    Science.gov (United States)

    Rip, Jason M K; McCann, Kevin S; Lynn, Denis H; Fawcett, Sonia

    2010-06-01

    Large-scale changes to the world's ecosystem are resulting in the deterioration of biostructure-the complex web of species interactions that make up ecological communities. A difficult, yet crucial task is to identify food web structures, or food web motifs, that are the building blocks of this baroque network of interactions. Once identified, these food web motifs can then be examined through experiments and theory to provide mechanistic explanations for how structure governs ecosystem stability. Here, we synthesize recent ecological research to show that generalist consumers coupling resources with different interaction strengths, is one such motif. This motif amazingly occurs across an enormous range of spatial scales, and so acts to distribute coupled weak and strong interactions throughout food webs. We then perform an experiment that illustrates the importance of this motif to ecological stability. We find that weak interactions coupled to strong interactions by generalist consumers dampen strong interaction strengths and increase community stability. This study takes a critical step by isolating a common food web motif and through clear, experimental manipulation, identifies the fundamental stabilizing consequences of this structure for ecological communities. PMID:20129988

  17. Efficient motif finding algorithms for large-alphabet inputs

    Directory of Open Access Journals (Sweden)

    Pavlovic Vladimir

    2010-10-01

    Full Text Available Abstract Background We consider the problem of identifying motifs, recurring or conserved patterns, in the biological sequence data sets. To solve this task, we present a new deterministic algorithm for finding patterns that are embedded as exact or inexact instances in all or most of the input strings. Results The proposed algorithm (1 improves search efficiency compared to existing algorithms, and (2 scales well with the size of alphabet. On a synthetic planted DNA motif finding problem our algorithm is over 10× more efficient than MITRA, PMSPrune, and RISOTTO for long motifs. Improvements are orders of magnitude higher in the same setting with large alphabets. On benchmark TF-binding site problems (FNP, CRP, LexA we observed reduction in running time of over 12×, with high detection accuracy. The algorithm was also successful in rapidly identifying protein motifs in Lipocalin, Zinc metallopeptidase, and supersecondary structure motifs for Cadherin and Immunoglobin families. Conclusions Our algorithm reduces computational complexity of the current motif finding algorithms and demonstrate strong running time improvements over existing exact algorithms, especially in important and difficult cases of large-alphabet sequences.

  18. Frequency patterns of T-cell exposed motifs in immunoglobulin heavy chain peptides presented by MHCs

    Directory of Open Access Journals (Sweden)

    Robert D. Bremel

    2014-10-01

    Full Text Available Immunoglobulins are highly diverse protein sequences that are processed and presented to T-cells by B-cells and other antigen presenting cells. We examined a large dataset of immunoglobulin heavy chain variable regions (IGHV to assess the diversity of T-cell exposed motifs (TCEM. TCEM comprise those amino acids in a MHC-bound peptide which face outwards, surrounded by the MHC histotope, and which engage the T-cell receptor. Within IGHV there is a distinct pattern of predicted MHC class II binding and a very high frequency of re-use of the TCEMs. The re-use frequency indicates that only a limited number of different cognate T-cells are required to engage many different clonal B-cells. The amino acids in each outward-facing TCEM are intercalated with the amino acids of inward-facing MHC groove-exposed motifs (GEM. Different GEM may have differing, allele-specific, MHC binding affinities. The intercalation of TCEM and GEM in a peptide allows for a vast combinatorial repertoire of epitopes, each eliciting a different response. Outcome of T-cell receptor binding is determined by overall signal strength, which is a function of the number of responding T-cells and the duration of engagement. Hence, the frequency of T-cell exposed motif re-use appears to be an important determinant of whether a T-cell response is stimulatory or suppressive. The frequency distribution of TCEMs implies that somatic hypermutation is followed by clonal expansion that develop along repeated pathways. The observations of TCEM and GEM derived from immunoglobulins suggest a relatively simple, yet powerful, mechanism to correlate T-cell polyspecificity, through re-use of TCEMs, with a very high degree of specificity achieved by combination with a diversity of GEMs. The frequency profile of TCEMs also points to an economical mechanism for maintaining T-cell memory, recall, and self-discrimination based on an endogenously generated profile of motifs.

  19. Common promoter elements in odorant and vomeronasal receptor genes.

    Directory of Open Access Journals (Sweden)

    Jussara S Michaloski

    Full Text Available In mammals, odorants and pheromones are detected by hundreds of odorant receptors (ORs and vomeronasal receptors (V1Rs and V2Rs expressed by sensory neurons that are respectively located in the main olfactory epithelium and in the vomeronasal organ. Even though these two olfactory systems are functionally and anatomically separate, their sensory neurons show a common mechanism of receptor gene regulation: each neuron expresses a single receptor gene from a single allele. The mechanisms underlying OR and VR gene expression remain unclear. Here we investigated if OR and V1R genes share common sequences in their promoter regions.We conducted a comparative analysis of promoter regions of 39 mouse V1R genes and found motifs that are common to a large number of promoters. We then searched mouse OR promoter regions for motifs that resemble the ones found in the V1R promoters. We identified motifs that are present in both the V1R and OR promoter regions. Some of these motifs correspond to the known O/E like binding sites while others resemble binding sites for transcriptional repressors. We show that one of these motifs specifically interacts with proteins extracted from both nuclei from olfactory and vomeronasal neurons. Our study is the first to identify motifs that resemble binding sites for repressors in the promoters of OR and V1R genes. Analysis of these motifs and of the proteins that bind to these motifs should reveal important aspects of the mechanisms of OR/V1R gene regulation.

  20. Microstructure and Oxidation Behavior of CNT/PyC/SiC Coating on C/C Composite Material

    OpenAIRE

    Mizuki, Hironori; Sano, Hideaki; Zheng, Guo-Bin; Uchiyama, Yasuo

    2008-01-01

    CNT/PyC/SiC coating were prepared by direct growth of CNTs on C/C followed by deposition of PyC (pyrolytic carbon) and SiC. It is found that the coating consisted of two layers; the CNT/PyC/SiC layer and SiC layer. The oxidation resistance of C/C was improved by the coating, which had much fewer cracks and better thermal-shock resistance.

  1. Direct conversion of cellulose using carbon monoxide and water on a Pt-Mo2C/C catalyst

    KAUST Repository

    Li, Jing

    2014-01-01

    CO and H2O were employed as the hydrogen source for cellulose conversion to polyols. Pt-Mo2C/C tandem catalyst with the Pt-Mo 2C domain responsible for H2 and/or H production and the Pt-C domain for cellulose conversion was fabricated. Considerable polyols were obtained over this tandem Pt-Mo2C/C catalyst. This journal is © 2014 The Royal Society of Chemistry.

  2. Simulation for F.C.C. deformation texture by modified pencil glide theory[Face Centered Cubic

    Energy Technology Data Exchange (ETDEWEB)

    Masui, H.

    1999-11-26

    Inspired by the pencil glide theory for b.c.c. metal, modified pencil glide theory for f.c.c. metal was proposed, dividing the 12 glide systems of f.c.c. metal into three groups individually composed of eight {l{underscore}brace}111{r{underscore}brace}{l{underscore}angle}110{r{underscore}angle} glide systems around the principal axes X[100], Y[010] and Z[001]. These assumptions yielded two mathematical solutions {Omega}(3) and {Omega}(1). In {Omega}(3), from the three groups with four complete conjugated glide systems composed of, respectively, two glide systems of common {l{underscore}angle}110{r{underscore}angle} direction, only one group with the maximum plastic work may operate if the requirements are satisfied, otherwise glide systems in {Omega}(1) where one of the four conjugated glide systems is zero are activated. The model considering the 12 glide systems of f.c.c. as a whole explained many experimentally stable orientations in axisymmetric and rolling deformation. The differences between the two pencil glide theories for b.c.c. and f.c.c. are also discussed with data.

  3. An intact PDZ motif is essential for correct P2Y12 purinoceptor traffic in human platelets.

    Science.gov (United States)

    Nisar, Shaista; Daly, Martina E; Federici, Augusto B; Artoni, Andrea; Mumford, Andrew D; Watson, Stephen P; Mundell, Stuart J

    2011-11-17

    The platelet P2Y(12) purinoceptor (P2Y(12)R), which plays a crucial role in hemostasis, undergoes internalization and subsequent recycling to maintain receptor responsiveness, processes that are essential for normal platelet function. Here, we observe that P2Y(12)R function is compromised after deletion or mutation of the 4 amino acids at the extreme C-terminus of this receptor (ETPM), a putative postsynaptic density 95/disc large/zonula occludens-1 (PDZ)-binding motif. In cell line models, removal of this sequence or mutation of one of its core residues (P341A), attenuates receptor internalization and receptor recycling back to the membrane, thereby blocking receptor resensitization. The physiologic significance of these findings in the regulation of platelet function is shown by identification of a patient with a heterozygous mutation in the PDZ binding sequence of their P2Y(12)R (P341A) that is associated with reduced expression of the P2Y(12)R on the cell surface. Importantly, platelets from this subject showed significantly compromised P2Y(12)R recycling, emphasizing the importance of the extreme C-terminus of this receptor to ensure correct receptor traffic. PMID:21937696

  4. Discovering motifs in ranked lists of DNA sequences.

    Directory of Open Access Journals (Sweden)

    Eran Eden

    2007-03-01

    Full Text Available Computational methods for discovery of sequence elements that are enriched in a target set compared with a background set are fundamental in molecular biology research. One example is the discovery of transcription factor binding motifs that are inferred from ChIP-chip (chromatin immuno-precipitation on a microarray measurements. Several major challenges in sequence motif discovery still require consideration: (i the need for a principled approach to partitioning the data into target and background sets; (ii the lack of rigorous models and of an exact p-value for measuring motif enrichment; (iii the need for an appropriate framework for accounting for motif multiplicity; (iv the tendency, in many of the existing methods, to report presumably significant motifs even when applied to randomly generated data. In this paper we present a statistical framework for discovering enriched sequence elements in ranked lists that resolves these four issues. We demonstrate the implementation of this framework in a software application, termed DRIM (discovery of rank imbalanced motifs, which identifies sequence motifs in lists of ranked DNA sequences. We applied DRIM to ChIP-chip and CpG methylation data and obtained the following results. (i Identification of 50 novel putative transcription factor (TF binding sites in yeast ChIP-chip data. The biological function of some of them was further investigated to gain new insights on transcription regulation networks in yeast. For example, our discoveries enable the elucidation of the network of the TF ARO80. Another finding concerns a systematic TF binding enhancement to sequences containing CA repeats. (ii Discovery of novel motifs in human cancer CpG methylation data. Remarkably, most of these motifs are similar to DNA sequence elements bound by the Polycomb complex that promotes histone methylation. Our findings thus support a model in which histone methylation and CpG methylation are mechanistically linked

  5. Fitting a mixture model by expectation maximization to discover motifs in biopolymers

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, T.L.; Elkan, C. [Univ. of California, La Jolla, CA (United States)

    1994-12-31

    The algorithm described in this paper discovers one or more motifs in a collection of DNA or protein sequences by using the technique of expectation maximization to fit a two-component finite mixture model to the set of sequences. Multiple motifs are found by fitting a mixture model to the data, probabilistically erasing the occurrences of the motif thus found, and repeating the process to find successive motifs. The algorithm requires only a set of unaligned sequences and a number specifying the width of the motifs as input. It returns a model of each motif and a threshold which together can be used as a Bayes-optimal classifier for searching for occurrences of the motif in other databases. The algorithm estimates how many times each motif occurs in each sequence in the dataset and outputs an alignment of the occurrences of the motif. The algorithm is capable of discovering several different motifs with differing numbers of occurrences in a single dataset.

  6. Cholesterol modulates bitter taste receptor function.

    Science.gov (United States)

    Pydi, Sai Prasad; Jafurulla, Md; Wai, Lisa; Bhullar, Rajinder P; Chelikani, Prashen; Chattopadhyay, Amitabha

    2016-09-01

    Bitter taste perception in humans is believed to act as a defense mechanism against ingestion of potential toxic substances. Bitter taste is perceived by 25 distinct bitter taste receptors (T2Rs) which belong to the family of G protein-coupled receptors (GPCRs). In the overall context of the role of membrane lipids in GPCR function, we show here that T2R4, a representative member of the bitter taste receptor family, displays cholesterol sensitivity in its signaling function. In order to gain further insight into cholesterol sensitivity of T2R4, we mutated two residues Tyr114(3.59) and Lys117(3.62) present in the cholesterol recognition amino acid consensus (CRAC) motif in T2R4 with alanines. We carried out functional characterization of the mutants by calcium mobilization, followed by cholesterol depletion and replenishment. CRAC motifs in GPCRs have previously been implicated in preferential cholesterol association. Our analysis shows that the CRAC motif represents an intrinsic feature of bitter taste receptors and is conserved in 22 out of 25 human T2Rs. We further demonstrate that Lys117, an important CRAC residue, is crucial in the reported cholesterol sensitivity of T2R4. Interestingly, cholesterol sensitivity of T2R4 was observed at quinine concentrations in the lower mM range. To the best of our knowledge, our results represent the first report addressing the molecular basis of cholesterol sensitivity in the function of taste receptors. PMID:27288892

  7. Effect of infiltrating Si on friction properties of C/C composites

    Institute of Scientific and Technical Information of China (English)

    马运柱; 黄伯云; 熊翔; 肖鹏; 李江鸿; 黄启忠; 易茂忠

    2003-01-01

    In order to improve the friction-wear properties of the C/C composites for aircraft brake pairs, the fric-tion behavior of samples with infiltrating Si was investigated. The influence of Si smearing thickness on frictionproperties was studied in detail. The results show that with the increase of Si smearing thickness and β-SiC content,the friction coefficient reduces from 0.40 to 0.30; the linear wear of stators increases from 2.0 μm to 18.9 μm percycle, and that of rotors increases from 1.4 μm to 22.6 μm per cycle; mass wear of stators increases from 20.6 mgto 126.9 mg per cycle, and that of rotors increases from 13.7 mg to 166.2 mg per cycle. On the other hand, whena large number of inhomogeneous β-SiC particulates are performed, friction surfaces of the samples flake off layer bylayer and many nicks are observed.

  8. Microbial aldolases as C-C bonding enzymes--unknown treasures and new developments.

    Science.gov (United States)

    Samland, Anne K; Sprenger, Georg A

    2006-07-01

    Aldolases are a specific group of lyases that catalyze the reversible stereoselective addition of a donor compound (nucleophile) onto an acceptor compound (electrophile). Whereas most aldolases are specific for their donor compound in the aldolization reaction, they often tolerate a wide range of aldehydes as acceptor compounds. C-C bonding by aldolases creates stereocenters in the resulting aldol products. This makes aldolases interesting tools for asymmetric syntheses of rare sugars or sugar-derived compounds as iminocyclitols, statins, epothilones, and sialic acids. Besides the well-known fructose 1,6-bisphosphate aldolase, other aldolases of microbial origin have attracted the interest of synthetic bio-organic chemists in recent years. These are either other dihydroxyacetone phosphate aldolases or aldolases depending on pyruvate/phosphoenolpyruvate, glycine, or acetaldehyde as donor substrate. Recently, an aldolase that accepts dihydroxyacetone or hydroxyacetone as a donor was described. A further enlargement of the arsenal of available chemoenzymatic tools can be achieved through screening for novel aldolase activities and directed evolution of existing aldolases to alter their substrate- or stereospecifities. We give an update of work on aldolases, with an emphasis on microbial aldolases. PMID:16614860

  9. Spectroscopic Characterization of Lanthanum-Mediated Dehydrogenation and C-C Bond Coupling of Ethylene.

    Science.gov (United States)

    Kumari, Sudesh; Cao, Wenjin; Zhang, Yuchen; Roudjane, Mourad; Yang, Dong-Sheng

    2016-07-01

    La(C2H2) and La(C4H6) are observed from the reaction of laser-vaporized La atoms with ethylene molecules by photoionization time-of-flight mass spectrometry and characterized by mass-analyzed threshold ionization spectroscopy. La(C2H2) is identified as a metallacyclopropene and La(C4H6) as a metallacyclopentene. The three-membered ring is formed by concerted H2 elimination and the five-membered cycle by dehydrogenation and C-C bond coupling. Both metallacycles prefer a doublet ground state with a La 6s-based unpaired electron. Ionization of the neutral doublet state of either complex produces a singlet ion state by removing the La-based electron. The ionization allows accurate measurements of the adiabatic ionization energy of the neutral doublet state and metal-ligand and ligand-based vibrational frequencies of the neutral and ionic states. Although the La atom is in a formal oxidation state of +2, the ionization energies of these metal-hydrocarbon cycles are lower than that of the neutral La atom. Deuteration has a small effect on the ionization energies of the two cyclic radicals but distinctive effects on their vibrational frequencies. PMID:27322131

  10. The Infiltration Process and Texture Transition of 2D C/C Composites

    Institute of Scientific and Technical Information of China (English)

    Hejun Li; Guozhong Xu; Kezhi Li; Chuang Wang; Wei Li; Miaoling Li

    2009-01-01

    2D needle-punched fiber felt was infiltrated by a kind of rapid isothermal chemical vapor infiltration technique. The infiltration process and texture transition of the infiltrated C/C composites were investigated. The porosity and the variations of the cumulative pore volume were determined by mercury porosimetry. The texture of matrix carbon was studied under a polarized light microscope. The results show that the relative mass gain of the sample increases directly as the infiltration time at the initial stage until 20 h, and subsequently the increasing rate of the relative mass gain decreases gradually with the prolonging of infiltration time. Three layers of pyrocarbon were formed around fibers. Low-textured pyrocarbon was obtained at the initial stage. With the densification going on, high-textured pyrocarbon was formed on the surface of low-textured pyrocarbon. Then, low-textured pyrocarbon was produced again during the final stage of densification. The texture transition is ascribed to the variation of the ratio of cumulative inner surface area to volume of pores and the gas partial pressure in pores.

  11. Mining Natural-Products Screening Data for Target-Class Chemical Motifs.

    Science.gov (United States)

    Coma, Isabel; Bandyopadhyay, Deepak; Diez, Emilio; Ruiz, Emilio Alvarez; de los Frailes, Maria Teresa; Colmenarejo, Gonzalo

    2014-06-01

    In this article, we describe two complementary data-mining approaches used to characterize the GlaxoSmithKline (GSK) natural-products set (NPS) based on information from the high-throughput screening (HTS) databases. Both methods rely on the aggregation and analysis of a large set of single-shot screening data for a number of biological assays, with the goal to reveal natural-product chemical motifs. One of them is an established method based on the data-driven clustering of compounds using a wide range of descriptors,(1)whereas the other method partitions and hierarchically clusters the data to identify chemical cores.(2,3)Both methods successfully find structural scaffolds that significantly hit different groups of discrete drug targets, compared with their relative frequency of demonstrating inhibitory activity in a large number of screens. We describe how these methods can be applied to unveil hidden information in large single-shot HTS data sets. Applied prospectively, this type of information could contribute to the design of new chemical templates for drug-target classes and guide synthetic efforts for lead optimization of tractable hits that are based on natural-product chemical motifs. Relevant findings for 7TM receptors (7TMRs), ion channels, class-7 transferases (protein kinases), hydrolases, and oxidoreductases will be discussed. PMID:24518065

  12. Mapracorat, a selective glucocorticoid receptor agonist, causes apoptosis of eosinophils infiltrating the conjunctiva in late-phase experimental ocular allergy

    Directory of Open Access Journals (Sweden)

    Baiula M

    2014-06-01

    Full Text Available Monica Baiula,1 Andrea Bedini,1 Jacopo Baldi,1 Megan E Cavet,2 Paolo Govoni,3 Santi Spampinato11Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy; 2Global Pharmaceutical R&D, Bausch & Lomb Inc., Rochester, NY, USA; 3Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, ItalyBackground: Mapracorat, a novel nonsteroidal selective glucocorticoid receptor agonist, has been proposed for the topical treatment of inflammatory disorders as it binds with high affinity and selectivity to the human glucocorticoid receptor and displays a potent anti-inflammatory activity, but seems to be less effective in transactivation of a number of genes, resulting in a lower potential for side effects. Contrary to classical glucocorticoids, mapracorat displays a reduced ability to increase intraocular pressure and in inducing myocilin, a protein linked to intraocular pressure elevation. Allergic conjunctivitis is the most common form of ocular allergy and can be divided into an early phase, developing immediately after allergen exposure and driven primarily by mast cell degranulation, and a late phase, developing from 6–10 hours after the antigen challenge, and characterized by conjunctival infiltration of eosinophils and other immune cells as well as by the production of cytokines and chemokines.Methods: In this study, mapracorat was administered into the conjunctival sac of ovalbumin (OVA-sensitized guinea pigs 2 hours after the induction of allergic conjunctivitis, with the aim of investigating its activity in reducing clinical signs of the late-phase ocular reaction and to determine its mechanism of anti-allergic effects with respect to apoptosis of conjunctival eosinophils and expression of the chemokines C-C motif ligand 5 (CCL5, C-C motif ligand 11 (CCL11, and interleukin-8 (IL-8 and the proinflammatory cytokines interleukin-1β (IL-1β and tumor necrosis factor-α (TNF

  13. Measurements of ionization and attachment coefficients in 0.468% and 4.910% c-C4F8/Ar mixtures and pure c-C4F8

    International Nuclear Information System (INIS)

    We measured the density normalized ionization coefficients and attachment coefficients in diluted c-C4F8/Ar mixtures and in pure perfluorocyclobutane (c-C4F8) by the steady-state Townsend method. The ionization coefficients in the mixture gas are almost equal to those in pure argon at the high E/N range but differ considerably at the low E/N range. The present coefficients in pure c-C4F8 agree well with previously reported values at the high E/N range, but there are significant differences at the low E/N range. Measurements in the low E/N range were difficult, and there are few data of the attachment coefficients

  14. Modeling Small Noncanonical RNA Motifs with the Rosetta FARFAR Server.

    Science.gov (United States)

    Yesselman, Joseph D; Das, Rhiju

    2016-01-01

    Noncanonical RNA motifs help define the vast complexity of RNA structure and function, and in many cases, these loops and junctions are on the order of only ten nucleotides in size. Unfortunately, despite their small size, there is no reliable method to determine the ensemble of lowest energy structures of junctions and loops at atomic accuracy. This chapter outlines straightforward protocols using a webserver for Rosetta Fragment Assembly of RNA with Full Atom Refinement (FARFAR) ( http://rosie.rosettacommons.org/rna_denovo/submit ) to model the 3D structure of small noncanonical RNA motifs for use in visualizing motifs and for further refinement or filtering with experimental data such as NMR chemical shifts. PMID:27665600

  15. PMS6MC: A Multicore Algorithm for Motif Discovery

    Directory of Open Access Journals (Sweden)

    Shibdas Bandyopadhyay

    2013-11-01

    Full Text Available We develop an efficient multicore algorithm, PMS6MC, for the (l; d-motif discovery problem in which we are to find all strings of length l that appear in every string of a given set of strings with at most d mismatches. PMS6MC is based on PMS6, which is currently the fastest single-core algorithm for motif discovery in large instances. The speedup, relative to PMS6, attained by our multicore algorithm ranges from a high of 6.62 for the (17,6 challenging instances to a low of 2.75 for the (13,4 challenging instances on an Intel 6-core system. We estimate that PMS6MC is 2 to 4 times faster than other parallel algorithms for motif search on large instances.

  16. Motifs in Triadic Random Graphs based on Steiner Triple Systems

    CERN Document Server

    Winkler, Marco

    2013-01-01

    Conventionally, pairwise relationships between nodes are considered to be the fundamental building blocks of complex networks. However, over the last decade the overabundance of certain sub-network patterns, so called motifs, has attracted high attention. It has been hypothesized, these motifs, instead of links, serve as the building blocks of network structures. Although the relation between a network's topology and the general properties of the system, such as its function, its robustness against perturbations, or its efficiency in spreading information is the central theme of network science, there is still a lack of sound generative models needed for testing the functional role of subgraph motifs. Our work aims to overcome this limitation. We employ the framework of exponential random graphs (ERGMs) to define novel models based on triadic substructures. The fact that only a small portion of triads can actually be set independently poses a challenge for the formulation of such models. To overcome this obst...

  17. How pathogens use linear motifs to perturb host cell networks

    KAUST Repository

    Via, Allegra

    2015-01-01

    Molecular mimicry is one of the powerful stratagems that pathogens employ to colonise their hosts and take advantage of host cell functions to guarantee their replication and dissemination. In particular, several viruses have evolved the ability to interact with host cell components through protein short linear motifs (SLiMs) that mimic host SLiMs, thus facilitating their internalisation and the manipulation of a wide range of cellular networks. Here we present convincing evidence from the literature that motif mimicry also represents an effective, widespread hijacking strategy in prokaryotic and eukaryotic parasites. Further insights into host motif mimicry would be of great help in the elucidation of the molecular mechanisms behind host cell invasion and the development of anti-infective therapeutic strategies.

  18. The Electronegativity Analysis of c-C4F8 as a Potential Insulation Substitute of SF6

    Science.gov (United States)

    Zhao, Xiaoling; Jiao, Juntao; Li, Bing; Xiao, Dengming

    2016-03-01

    The density distributions related to gas electronegativity for c-C4F8 gas, including negative ion, electron number and electron energy densities in the discharge process, are derived theoretically in both plane-to-plane and point-to-plane electrode geometries. These calculations have been performed through the Boltzmann equation in the condition of a steady-state Townsend (SST) experiment and a fluid model in the condition of both uniform and non-uniform electric fields. The electronegativity coefficients a = n-/ne of c-C4F8 and SF6 are compared to further describe the electron affinity of c-C4F8. The result shows that c-C4F8 represents an obvious electron-attachment performance in the discharge process. However, c-C4F8 still has much weaker gas electronegativity than SF6, whose electronegativity coefficient is lower than that of SF6 by at least three orders of magnitude. supported by National Natural Science Foundation of China (No. 51337006)

  19. A Numerical Study on the Thermal Conductivity of 3D Woven C/C Composites at High Temperature

    Science.gov (United States)

    Shigang, Ai; Rujie, He; Yongmao, Pei

    2015-12-01

    Experimental data for Carbon/Carbon (C/C) constituent materials are combined with a three dimensional steady state heat transfer finite element analysis to demonstrate the average in-plane and out-of-plane thermal conductivities (TCs) of C/C composites. The finite element analysis is carried out at two distinct length scales: (a) a micro scale comparable with the diameter of carbon fibres and (b) a meso scale comparable with the carbon fibre yarns. Micro-scale model calculate the TCs at the fibre yarn scale in the three orthogonal directions ( x, y and z). The output results from the micro-scale model are then incorporated in the meso-scale model to obtain the global TCs of the 3D C/C composite. The simulation results are quite consistent with the theoretical and experimental counterparts reported in references. Based on the numerical approach, TCs of the 3D C/C composite are calculated from 300 to 2500 K. Particular attention is given in elucidating the variations of the TCs with temperature. The multi-scale models provide an efficient approach to predict the TCs of 3D textile materials, which is helpful for the thermodynamic property analysis and structure design of the C/C composites.

  20. Selection against spurious promoter motifs correlates withtranslational efficiency across bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Froula, Jeffrey L.; Francino, M. Pilar

    2007-05-01

    Because binding of RNAP to misplaced sites could compromise the efficiency of transcription, natural selection for the optimization of gene expression should regulate the distribution of DNA motifs capable of RNAP-binding across the genome. Here we analyze the distribution of the -10 promoter motifs that bind the {sigma}{sup 70} subunit of RNAP in 42 bacterial genomes. We show that selection on these motifs operates across the genome, maintaining an over-representation of -10 motifs in regulatory sequences while eliminating them from the nonfunctional and, in most cases, from the protein coding regions. In some genomes, however, -10 sites are over-represented in the coding sequences; these sites could induce pauses effecting regulatory roles throughout the length of a transcriptional unit. For nonfunctional sequences, the extent of motif under-representation varies across genomes in a manner that broadly correlates with the number of tRNA genes, a good indicator of translational speed and growth rate. This suggests that minimizing the time invested in gene transcription is an important selective pressure against spurious binding. However, selection against spurious binding is detectable in the reduced genomes of host-restricted bacteria that grow at slow rates, indicating that components of efficiency other than speed may also be important. Minimizing the number of RNAP molecules per cell required for transcription, and the corresponding energetic expense, may be most relevant in slow growers. These results indicate that genome-level properties affecting the efficiency of transcription and translation can respond in an integrated manner to optimize gene expression. The detection of selection against promoter motifs in nonfunctional regions also implies that no sequence may evolve free of selective constraints, at least in the relatively small and unstructured genomes of bacteria.

  1. The Reovirus Sigmal Aspartic Acid Sandwich: A Trimerization Motif Poised for Conformational Change

    Energy Technology Data Exchange (ETDEWEB)

    Schelling,P.; Guglielml, K.; Kirchner, E.; Paetzold, b.; Dermody, T.; Stehle, T.

    2007-01-01

    Reovirus attachment protein {sigma}1 mediates engagement of receptors on the surface of target cells and undergoes dramatic conformational rearrangements during viral disassembly in the endocytic pathway. The {sigma}1 protein is a filamentous, trimeric molecule with a globular {beta}-barrel head domain. An unusual cluster of aspartic acid residues sandwiched between hydrophobic tyrosines is located at the {sigma}1 subunit interface. A 1.75 {angstrom} structure of the {sigma}1 head domain now reveals two water molecules at the subunit interface that are held strictly in position and interact with neighboring residues. Structural and biochemical analyses of mutants affecting the aspartic acid sandwich indicate that these residues and the corresponding chelated water molecules act as a plug to block the free flow of solvent and stabilize the trimer. This arrangement of residues at the {sigma}1 head trimer interface illustrates a new protein design motif that may confer conformational mobility during cell entry.

  2. The reovirus sigma1 aspartic acid sandwich: a trimerization motif poised for conformational change.

    Science.gov (United States)

    Schelling, Pierre; Guglielmi, Kristen M; Kirchner, Eva; Paetzold, Bernhard; Dermody, Terence S; Stehle, Thilo

    2007-04-13

    Reovirus attachment protein sigma1 mediates engagement of receptors on the surface of target cells and undergoes dramatic conformational rearrangements during viral disassembly in the endocytic pathway. The sigma1 protein is a filamentous, trimeric molecule with a globular beta-barrel head domain. An unusual cluster of aspartic acid residues sandwiched between hydrophobic tyrosines is located at the sigma1 subunit interface. A 1.75-A structure of the sigma1 head domain now reveals two water molecules at the subunit interface that are held strictly in position and interact with neighboring residues. Structural and biochemical analyses of mutants affecting the aspartic acid sandwich indicate that these residues and the corresponding chelated water molecules act as a plug to block the free flow of solvent and stabilize the trimer. This arrangement of residues at the sigma1 head trimer interface illustrates a new protein design motif that may confer conformational mobility during cell entry.

  3. Zavorne ploščice iz karboniziranega materiala za zavorne diske iz C/C-SiC: Carbonised-material-based brake pads for a C/C-SiC composite brake disc:

    OpenAIRE

    Stadler, Zmago

    2001-01-01

    Letely the brake discs from carbon-fibre-reinforced carbon composites infiltrated by silicon (LSI-process) have become very interesting for automotive brakes applications. Composite materials with a hard SiC layer on the surface of the disc (C/C-SiC) or composites with the fibre-reinforced ceramic structure (C/SiC) need the right brake-lining materials. The results of our new-brake-lining-material investigation for C/C-SiC brake discs are presented. The influence of some particular additives ...

  4. Some results on more flexible versions of Graph Motif

    CERN Document Server

    Rizzi, Romeo

    2012-01-01

    The problems studied in this paper originate from Graph Motif, a problem introduced in 2006 in the context of biological networks. Informally speaking, it consists in deciding if a multiset of colors occurs in a connected subgraph of a vertex-colored graph. Due to the high rate of noise in the biological data, more flexible definitions of the problem have been outlined. We present in this paper two inapproximability results for two different optimization variants of Graph Motif. We also study another definition of the problem, when the connectivity constraint is replaced by modularity. While the problem stays NP-complete, it allows algorithms in FPT for biologically relevant parameterizations.

  5. iLIR database: A web resource for LIR motif-containing proteins in eukaryotes

    Science.gov (United States)

    Jacomin, Anne-Claire; Samavedam, Siva; Promponas, Vasilis; Nezis, Ioannis P.

    2016-01-01

    ABSTRACT Atg8-family proteins are the best-studied proteins of the core autophagic machinery. They are essential for the elongation and closure of the phagophore into a proper autophagosome. Moreover, Atg8-family proteins are associated with the phagophore from the initiation of the autophagic process to, or just prior to, the fusion between autophagosomes with lysosomes. In addition to their implication in autophagosome biogenesis, they are crucial for selective autophagy through their ability to interact with selective autophagy receptor proteins necessary for the specific targeting of substrates for autophagic degradation. In the past few years it has been revealed that Atg8-interacting proteins include not only receptors but also components of the core autophagic machinery, proteins associated with vesicles and their transport, and specific proteins that are selectively degraded by autophagy. Atg8-interacting proteins contain a short linear LC3-interacting region/LC3 recognition sequence/Atg8-interacting motif (LIR/LRS/AIM) motif which is responsible for their interaction with Atg8-family proteins. These proteins are referred to as LIR-containing proteins (LIRCPs). So far, many experimental efforts have been carried out to identify new LIRCPs, leading to the characterization of some of them in the past 10 years. Given the need for the identification of LIRCPs in various organisms, we developed the iLIR database (https://ilir.warwick.ac.uk) as a freely available web resource, listing all the putative canonical LIRCPs identified in silico in the proteomes of 8 model organisms using the iLIR server, combined with a Gene Ontology (GO) term analysis. Additionally, a curated text-mining analysis of the literature permitted us to identify novel putative LICRPs in mammals that have not previously been associated with autophagy. PMID:27484196

  6. Wet Friction and Wear Properties of C/C-SiC Composites During Different Braking Speeds%C/C-SiC材料不同制动速率下的湿式摩擦磨损性能

    Institute of Scientific and Technical Information of China (English)

    李专; 肖鹏; 岳静; 熊翔

    2013-01-01

    以炭纤维针刺毡为预制体,先采用化学气相渗透法制备炭基体,然后采用熔融渗硅法制备SiC基体,得到C/C-SiC摩擦材料;利用MM-1000型惯性试验台研究了C/C-SiC材料在不同制动速度下干态和CD15W-40柴油机油润滑状态下的摩擦磨损性能.研究结果表明:C/C-SiC摩擦材料与水的接触角为80.5°左右,为亲油性材料;C/C-SiC材料在CD15W40柴油机油润滑状态下,随制动速度从3000r/min升高到6000r/min,其摩擦因数和线性磨损量在4000r/min时达到最大值,分别是0.21μm/cycle和1.1μm/cycle,而在5000r/min和6000r/min时,其摩擦因数均为0.17,线性磨损量均为0;C/C-SiC摩擦材料在湿态条件下能保持较高的摩擦因数,制动曲线平稳,磨损率低,可作为新一代工程机械和重型车辆湿式离合器用摩擦材料的候选材料.%Carbon fibre reinforced carbon and silicon carbide dual matrix composites (C/C-SiC) were fabricated by the combination of chemical vapor infiltration (CVI) with liquid silicon infiltration (LSI). The tribological behaviors of the C/C-SiC composite were investigated using an MM-1000 friction and wear tester, at different braking speeds under dry and machine oil lubricating conditions. The results indicate that the contact angle between C/C-SiC and distilled water is about 80. 5°, which means the C/C-SiC are lipophilic materials. In the CD15W-40 diesel engine oil lubrication condition, with the brake speeds increasing from 3000r/min to 6000r/min, the coefficient of friction (COF) and linear wear of C/C-SiC reach the maximum value of 0. 21μm/cycle and 1. lμm/cycle respectively, at 4000r/min. When the brake speeds are 5000r/min and 6000r/min, the COF and the linear wear are 0. 17 and 0, respectively. C/C-SiC maintains a relatively high COF, smooth braking curves and lower wear rate in wet conditions, which can be used as candidate materials for wet clutch of new generation of construction machinery and heavy vehicles.

  7. Observation of Spontaneous C=C Bond Breaking in the Reaction between Atomic Boron and Ethylene in Solid Neon.

    Science.gov (United States)

    Jian, Jiwen; Lin, Hailu; Luo, Mingbiao; Chen, Mohua; Zhou, Mingfei

    2016-07-11

    A ground-state boron atom inserts into the C=C bond of ethylene to spontaneously form the allene-like compound H2 CBCH2 on annealing in solid neon. This compound can further isomerize to the propyne-like HCBCH3 isomer under UV light excitation. The observation of this unique spontaneous C=C bond insertion reaction is consistent with theoretical predictions that the reaction is thermodynamically exothermic and kinetically facile. This work demonstrates that the stronger C=C bond, rather than the less inert C-H bond, can be broken to form organoboron species from the reaction of a boron atom with ethylene even at cryogenic temperatures.

  8. Observation of Spontaneous C=C Bond Breaking in the Reaction between Atomic Boron and Ethylene in Solid Neon.

    Science.gov (United States)

    Jian, Jiwen; Lin, Hailu; Luo, Mingbiao; Chen, Mohua; Zhou, Mingfei

    2016-07-11

    A ground-state boron atom inserts into the C=C bond of ethylene to spontaneously form the allene-like compound H2 CBCH2 on annealing in solid neon. This compound can further isomerize to the propyne-like HCBCH3 isomer under UV light excitation. The observation of this unique spontaneous C=C bond insertion reaction is consistent with theoretical predictions that the reaction is thermodynamically exothermic and kinetically facile. This work demonstrates that the stronger C=C bond, rather than the less inert C-H bond, can be broken to form organoboron species from the reaction of a boron atom with ethylene even at cryogenic temperatures. PMID:27240114

  9. Effects of ion irradiation on the hardness properties of graphites and C/C composites by indentation tests

    International Nuclear Information System (INIS)

    Small blocks of graphite and C/C composite materials were argon ion irradiated. The load-depth curves were obtained from the micro indentation tests before and after ion irradiation. For the C/C composite material, the indentation test was also performed perpendicular to the depth direction of ion irradiation and the distribution of the hardness properties was examined in the depth direction. As a result, hardness properties of the carbon materials were able to be expressed as a function of dpa values

  10. Positional bias of general and tissue-specific regulatory motifs in mouse gene promoters

    Directory of Open Access Journals (Sweden)

    Farré Domènec

    2007-12-01

    Full Text Available Abstract Background The arrangement of regulatory motifs in gene promoters, or promoter architecture, is the result of mutation and selection processes that have operated over many millions of years. In mammals, tissue-specific transcriptional regulation is related to the presence of specific protein-interacting DNA motifs in gene promoters. However, little is known about the relative location and spacing of these motifs. To fill this gap, we have performed a systematic search for motifs that show significant bias at specific promoter locations in a large collection of housekeeping and tissue-specific genes. Results We observe that promoters driving housekeeping gene expression are enriched in particular motifs with strong positional bias, such as YY1, which are of little relevance in promoters driving tissue-specific expression. We also identify a large number of motifs that show positional bias in genes expressed in a highly tissue-specific manner. They include well-known tissue-specific motifs, such as HNF1 and HNF4 motifs in liver, kidney and small intestine, or RFX motifs in testis, as well as many potentially novel regulatory motifs. Based on this analysis, we provide predictions for 559 tissue-specific motifs in mouse gene promoters. Conclusion The study shows that motif positional bias is an important feature of mammalian proximal promoters and that it affects both general and tissue-specific motifs. Motif positional constraints define very distinct promoter architectures depending on breadth of expression and type of tissue.

  11. How curved membranes recruit amphipathic helices and protein anchoring motifs

    DEFF Research Database (Denmark)

    Hatzakis, Nikos; Bhatia, Vikram Kjøller; Larsen, Jannik;

    2009-01-01

    Lipids and several specialized proteins are thought to be able to sense the curvature of membranes (MC). Here we used quantitative fluorescence microscopy to measure curvature-selective binding of amphipathic motifs on single liposomes 50-700 nm in diameter. Our results revealed that sensing is p...

  12. Motifs in triadic random graphs based on Steiner triple systems

    Science.gov (United States)

    Winkler, Marco; Reichardt, Jörg

    2013-08-01

    Conventionally, pairwise relationships between nodes are considered to be the fundamental building blocks of complex networks. However, over the last decade, the overabundance of certain subnetwork patterns, i.e., the so-called motifs, has attracted much attention. It has been hypothesized that these motifs, instead of links, serve as the building blocks of network structures. Although the relation between a network's topology and the general properties of the system, such as its function, its robustness against perturbations, or its efficiency in spreading information, is the central theme of network science, there is still a lack of sound generative models needed for testing the functional role of subgraph motifs. Our work aims to overcome this limitation. We employ the framework of exponential random graph models (ERGMs) to define models based on triadic substructures. The fact that only a small portion of triads can actually be set independently poses a challenge for the formulation of such models. To overcome this obstacle, we use Steiner triple systems (STSs). These are partitions of sets of nodes into pair-disjoint triads, which thus can be specified independently. Combining the concepts of ERGMs and STSs, we suggest generative models capable of generating ensembles of networks with nontrivial triadic Z-score profiles. Further, we discover inevitable correlations between the abundance of triad patterns, which occur solely for statistical reasons and need to be taken into account when discussing the functional implications of motif statistics. Moreover, we calculate the degree distributions of our triadic random graphs analytically.

  13. Themes or Motifs? Aiming for Coherence through Interdisciplinary Outlines.

    Science.gov (United States)

    Barton, Keith C.; Smith Lynne A.

    2000-01-01

    Describes how "motif-units" undermine the potential benefits of integrated thematic instruction. Suggests replacing the term "thematic unit" with the concept of "interdisciplinary outline," which focus on meaningful content, authentic activities, students' needs, teacher mediation, and a variety of resources. Shows how one fourth-grade teacher…

  14. Linear motif atlas for phosphorylation-dependent signaling

    DEFF Research Database (Denmark)

    Miller, Martin Lee; Jensen, LJ; Diella, F;

    2008-01-01

    Systematic and quantitative analysis of protein phosphorylation is revealing dynamic regulatory networks underlying cellular responses to environmental cues. However, matching these sites to the kinases that phosphorylate them and the phosphorylation-dependent binding domains that may subsequently...... sequence models of linear motifs. The atlas is available as a community resource (http://netphorest.info)....

  15. Cloning and expression analysis of human reticulon 4c cDNA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    RTNs (reticulons) is a gene family related to the growth and differentiation of neuroendocrine cell. This family is composed of several members such as RTN1, RTN2 and RTN3. RTN1 and RTN2 have been proved to have 3 transcripts with different length. Because the RTN1c cDNA was involved in the sologenesis of small cell lung carcinoma (SCLC), it was selected as a bioinformatic probe to clone novel members of RTN family with the electric hybridization assistant new-gene cloning method (EHAC). A 1677-bp cDNA was identified from human brain cDNA library. The cDNA contains an intact open reading frame (ORF) which encodes a protein of 199 amino acids. This deduced protein is highly homologous to RTN1c, RTN2c and RTN3 with identities of 64.4%, 45.8% and 50.0% respectively. This new gene was named RTN4c (GenBank accession number: AF087901). Northern hybridization showed that the full length of RTN4c transcript is about 1.8 kb. It is hardly expressed in heart, placenta, lung, spleen, thymus, testis, ovary, small intestine and peripheral blood white cells; but it is highly expressed in the tissues of skeletal muscle, brain, liver and kidney, and less expressed in the pancreas, prostate and colon. Furthermore, Northern results also showed that there is a 2.3 kb transcript expressed in 14 tissues except liver and skeletal muscle; while another 5.0 kb transcript in brain, skeletal muscle and testis. By the electric hybridization walking, we obtained two full-length contigs with a length of 4632 and 2235 bp respectively. The former encodes a protein with 1192 amino acids and was defined as RTN4a; the latter encodes another protein with 373 amino acids, and was named RTN4b. The RTN4 gene was mapped to human chromosome 2p14-p13 region by the radiation hybridization (RH).

  16. Variable structure motifs for transcription factor binding sites

    Directory of Open Access Journals (Sweden)

    Wernisch Lorenz

    2010-01-01

    Full Text Available Abstract Background Classically, models of DNA-transcription factor binding sites (TFBSs have been based on relatively few known instances and have treated them as sites of fixed length using position weight matrices (PWMs. Various extensions to this model have been proposed, most of which take account of dependencies between the bases in the binding sites. However, some transcription factors are known to exhibit some flexibility and bind to DNA in more than one possible physical configuration. In some cases this variation is known to affect the function of binding sites. With the increasing volume of ChIP-seq data available it is now possible to investigate models that incorporate this flexibility. Previous work on variable length models has been constrained by: a focus on specific zinc finger proteins in yeast using restrictive models; a reliance on hand-crafted models for just one transcription factor at a time; and a lack of evaluation on realistically sized data sets. Results We re-analysed binding sites from the TRANSFAC database and found motivating examples where our new variable length model provides a better fit. We analysed several ChIP-seq data sets with a novel motif search algorithm and compared the results to one of the best standard PWM finders and a recently developed alternative method for finding motifs of variable structure. All the methods performed comparably in held-out cross validation tests. Known motifs of variable structure were recovered for p53, Stat5a and Stat5b. In addition our method recovered a novel generalised version of an existing PWM for Sp1 that allows for variable length binding. This motif improved classification performance. Conclusions We have presented a new gapped PWM model for variable length DNA binding sites that is not too restrictive nor over-parameterised. Our comparison with existing tools shows that on average it does not have better predictive accuracy than existing methods. However, it does

  17. GIT1 Paxillin-binding Domain Is a Four-helix Bundle, and It Binds to Both Paxillin LD2 and LD4 Motifs*S⃞

    OpenAIRE

    Zhang, Ziwei M.; Simmerman, Joseph A.; Guibao, Cristina D.; Zheng, Jie J.

    2008-01-01

    The G protein-coupled receptor kinase-interacting protein 1 (GIT1) is a multidomain protein that plays an important role in cell adhesion, motility, cytoskeletal remodeling, and membrane trafficking. GIT1 mediates the localization of the p21-activated kinase (PAK) and PAK-interactive exchange factor to focal adhesions, and its activation is regulated by the interaction between its C-terminal paxillin-binding domain (PBD) and the LD motifs of paxillin. In this study, we...

  18. NCBI nr-aa BLAST: CBRC-PCAP-01-1446 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PCAP-01-1446 ref|NP_001033695.1| chemokine (C-C motif) receptor 1 [Canis lupus... familiaris] dbj|BAE66670.1| chemokine (C-C motif) receptor 1 [Canis lupus familiaris] NP_001033695.1 1e-155 77% ...

  19. Molecular determinants of odorant receptor function in insects

    Indian Academy of Sciences (India)

    Anandasankar Ray; Wynand Van Der Goes Van Naters; John R Carlson

    2014-09-01

    The olfactory system of Drosophila melanogaster provides a powerful model to study molecular and cellular mechanisms underlying function of a sensory system. In the 1970s Siddiqi and colleagues pioneered the application of genetics to olfactory research and isolated several mutant Drosophila with odorant-specific defects in olfactory behaviour, suggesting that odorants are detected differentially by the olfactory system. Since then basic principles of olfactory system function and development have emerged using Drosophila as a model. Nearly four decades later we can add computational methods to further our understanding of how specific odorants are detected by receptors. Using a comparative approach we identify two categories of short amino acid sequence motifs: ones that are conserved family-wide predominantly in the C-terminal half of most receptors, and ones that are present in receptors that detect a specific odorant, 4-methylphenol, found predominantly in the N-terminal half. The odorant-specific sequence motifs are predictors of phenol detection in Anopheles gambiae and other insects, suggesting they are likely to participate in odorant binding. Conversely, the family-wide motifs are expected to participate in shared functions across all receptors and a mutation in the most conserved motif leads to a reduction in odor response. These findings lay a foundation for investigating functional domains within odorant receptors that can lead to a molecular understanding of odor detection.

  20. Epstein Barr virus/complement C3d receptor is an interferon alpha receptor.

    OpenAIRE

    Delcayre, A X; Salas, F.; Mathur, S; Kovats, K; Lotz, M.; Lernhardt, W

    1991-01-01

    Interferon alpha contains a sequence motif similar to the complement receptor type two (CR2/CD21) binding site on complement fragment C3d. Antibodies against a peptide with the CR2 binding sequence on C3d react with a peptide carrying the IFN alpha CR2 binding motif (residues 92-99) and with recombinant IFN alpha. The IFN alpha-derived peptide, as well as recombinant IFN alpha, inhibits C3bi/C3d interaction with CR2 on the Burkitt lymphoma Raji. The direct interaction of IFN alpha and CR2 is ...

  1. Highly Conductive, Mechanically Robust, and Electrochemically Inactive TiC/C Nanofiber Scaffold for High-Performance Silicon Anode Batteries

    KAUST Repository

    Yao, Yan

    2011-10-25

    Silicon has a high specific capacity of 4200 mAh/g as lithium-ion battery anodes, but its rapid capacity fading due to >300% volume expansion and pulverization presents a significant challenge for practical applications. Here we report a core-shell TiC/C/Si inactive/active nanocomposite for Si anodes demonstrating high specific capacity and excellent electrochemical cycling. The amorphous silicon layer serves as the active material to store Li+, while the inactive TiC/C nanofibers act as a conductive and mechanically robust scaffold for electron transport during the Li-Si alloying process. The core-shell TiC/C/Si nanocomposite anode shows ∼3000 mAh g-1 discharge capacity and 92% capacity retention after 100 charge/discharge cycles. The excellent cycling stability and high rate performance could be attributed to the tapering of the nanofibers and the open structure that allows facile Li ion transport and the high conductivity and mechanical stability of the TiC/C scaffold. © 2011 American Chemical Society.

  2. Computer Simulation of the E.C.C.S. Buckling Curve using a Monte-Carlo Method

    NARCIS (Netherlands)

    Strating, J.; Vos, H.

    1973-01-01

    The application of a Monte-Carlo simulation procedure to obtain the distribution function of the maximum load of a hinged column with imperfections is discussed. Buckling tests carried out by the E.C.C.S. on IPE 160 sections have been simulated. Information concerning the column variables is obtaine

  3. Silver(I) NHC mediated C-C bond activation of alkyl nitriles and catalytic efficiency in oxazoline synthesis.

    Science.gov (United States)

    Heath, Rachael; Müller-Bunz, Helge; Albrecht, Martin

    2015-05-21

    Preparation of silver triazolylidene (trz) species from triazolium salts and Ag2O in refluxing MeCN leads to a selective C-C bond cleavage and the formation of complexes of general formula [(trz)Ag(CN)] from Calkyl-CN bond activation. Moreover, these silver carbene complexes are precursors of highly active catalysts for oxazoline formation via aldol condensation. PMID:25913007

  4. 76 FR 39254 - Airworthiness Directives; Schweizer Aircraft Corporation (Schweizer) Model 269A, A-1, B, C, C-1...

    Science.gov (United States)

    2011-07-06

    ... Regulatory Policies and Procedures (44 FR 11034, February 26, 1979), (3) Will not affect intrastate aviation... Corporation (Schweizer) Model 269A, A-1, B, C, C-1, and TH-55 Series Helicopters AGENCY: Federal Aviation... reviewed Schweizer Service Bulletins No. B-295 for Model 269A, A-1, B, and C helicopters, and No....

  5. A mild route to mesoporous Mo2C-C hybrid nanospheres for high performance lithium-ion batteries

    Science.gov (United States)

    Gao, Qing; Zhao, Xinyu; Xiao, Ying; Zhao, Di; Cao, Minhua

    2014-05-01

    In this work, we have developed a mild route to fabricate typically mesoporous Mo2C-C hybrid nanospheres based on a solvothermal synthesis and reduction-carbonization process. This work opens a low-temperature route to synthesize valuable carbides. The resultant Mo2C-C hybrid, for the first time, is used as an anode material in lithium ion batteries (LIBs). Compared with bulk Mo2C, the Mo2C-C hybrid exhibits much better electrochemical performance. Remarkably, the hybrid electrode can deliver a specific capacity of over 670 mA h g-1 after 50 cycles at 100 mA g-1, which is much higher than that of the bulk material (113 mA h g-1). Even cycled at a high current density of 1000 mA g-1, high capacities of around 400-470 mA h g-1 can still be retained for the Mo2C-C hybrid. It might benefit from the synergistic effect of the nanohybridization, effectively relieving the volume change during the repeated lithium insertion-extraction reactions and maintaining the integrity of the electrical connections. It is expected that the present synthesis strategy for the Mo2C-C hybrid can be extended to other nanostructured carbides with good energy storage performance.In this work, we have developed a mild route to fabricate typically mesoporous Mo2C-C hybrid nanospheres based on a solvothermal synthesis and reduction-carbonization process. This work opens a low-temperature route to synthesize valuable carbides. The resultant Mo2C-C hybrid, for the first time, is used as an anode material in lithium ion batteries (LIBs). Compared with bulk Mo2C, the Mo2C-C hybrid exhibits much better electrochemical performance. Remarkably, the hybrid electrode can deliver a specific capacity of over 670 mA h g-1 after 50 cycles at 100 mA g-1, which is much higher than that of the bulk material (113 mA h g-1). Even cycled at a high current density of 1000 mA g-1, high capacities of around 400-470 mA h g-1 can still be retained for the Mo2C-C hybrid. It might benefit from the synergistic effect of

  6. Composite motifs integrating multiple protein structures increase sensitivity for function prediction.

    Science.gov (United States)

    Chen, Brian Y; Bryant, Drew H; Cruess, Amanda E; Bylund, Joseph H; Fofanov, Viacheslav Y; Kristensen, David M; Kimmel, Marek; Lichtarge, Olivier; Kavraki, Lydia E

    2007-01-01

    The study of disease often hinges on the biological function of proteins, but determining protein function is a difficult experimental process. To minimize duplicated effort, algorithms for function prediction seek characteristics indicative of possible protein function. One approach is to identify substructural matches of geometric and chemical similarity between motifs representing known active sites and target protein structures with unknown function. In earlier work, statistically significant matches of certain effective motifs have identified functionally related active sites. Effective motifs must be carefully designed to maintain similarity to functionally related sites (sensitivity) and avoid incidental similarities to functionally unrelated protein geometry (specificity). Existing motif design techniques use the geometry of a single protein structure. Poor selection of this structure can limit motif effectiveness if the selected functional site lacks similarity to functionally related sites. To address this problem, this paper presents composite motifs, which combine structures of functionally related active sites to potentially increase sensitivity. Our experimentation compares the effectiveness of composite motifs with simple motifs designed from single protein structures. On six distinct families of functionally related proteins, leave-one-out testing showed that composite motifs had sensitivity comparable to the most sensitive of all simple motifs and specificity comparable to the average simple motif. On our data set, we observed that composite motifs simultaneously capture variations in active site conformation, diminish the problem of selecting motif structures, and enable the fusion of protein structures from diverse data sources. PMID:17951837

  7. Endoplasmic reticulum protein targeting of phospholamban: a common role for an N-terminal di-arginine motif in ER retention?

    Directory of Open Access Journals (Sweden)

    Parveen Sharma

    Full Text Available BACKGROUND: Phospholamban (PLN is an effective inhibitor of the sarco(endoplasmic reticulum Ca(2+-ATPase, which transports Ca(2+ into the SR lumen, leading to muscle relaxation. A mutation of PLN in which one of the di-arginine residues at positions 13 and 14 was deleted led to a severe, early onset dilated cardiomyopathy. Here we were interested in determining the cellular mechanisms involved in this disease-causing mutation. METHODOLOGY/PRINCIPAL FINDING: Mutations deleting codons for either or both Arg13 or Arg14 resulted in the mislocalization of PLN from the ER. Our data show that PLN is recycled via the retrograde Golgi to ER membrane traffic pathway involving COP-I vesicles, since co-immunoprecipitation assays determined that COP I interactions are dependent on an intact di-arginine motif as PLN RDelta14 did not co-precipitate with COP I containing vesicles. Bioinformatic analysis determined that the di-arginine motif is present in the first 25 residues in a large number of all ER/SR Gene Ontology (GO annotated proteins. Mutations in the di-arginine motif of the Sigma 1-type opioid receptor, the beta-subunit of the signal recognition particle receptor, and Sterol-O-acyltransferase, three proteins identified in our bioinformatic screen also caused mislocalization of these known ER-resident proteins. CONCLUSION: We conclude that PLN is enriched in the ER due to COP I-mediated transport that is dependent on its intact di-arginine motif and that the N-terminal di-arginine motif may act as a general ER retrieval sequence.

  8. FPGA implementation of motifs-based neuronal network and synchronization analysis

    Science.gov (United States)

    Deng, Bin; Zhu, Zechen; Yang, Shuangming; Wei, Xile; Wang, Jiang; Yu, Haitao

    2016-06-01

    Motifs in complex networks play a crucial role in determining the brain functions. In this paper, 13 kinds of motifs are implemented with Field Programmable Gate Array (FPGA) to investigate the relationships between the networks properties and motifs properties. We use discretization method and pipelined architecture to construct various motifs with Hindmarsh-Rose (HR) neuron as the node model. We also build a small-world network based on these motifs and conduct the synchronization analysis of motifs as well as the constructed network. We find that the synchronization properties of motif determine that of motif-based small-world network, which demonstrates effectiveness of our proposed hardware simulation platform. By imitation of some vital nuclei in the brain to generate normal discharges, our proposed FPGA-based artificial neuronal networks have the potential to replace the injured nuclei to complete the brain function in the treatment of Parkinson's disease and epilepsy.

  9. A Bioinformatics Approach for Detecting Repetitive Nested Motifs using Pattern Matching

    Science.gov (United States)

    Romero, José R.; Carballido, Jessica A.; Garbus, Ingrid; Echenique, Viviana C.; Ponzoni, Ignacio

    2016-01-01

    The identification of nested motifs in genomic sequences is a complex computational problem. The detection of these patterns is important to allow the discovery of transposable element (TE) insertions, incomplete reverse transcripts, deletions, and/or mutations. In this study, a de novo strategy for detecting patterns that represent nested motifs was designed based on exhaustive searches for pairs of motifs and combinatorial pattern analysis. These patterns can be grouped into three categories, motifs within other motifs, motifs flanked by other motifs, and motifs of large size. The methodology used in this study, applied to genomic sequences from the plant species Aegilops tauschii and Oryza sativa, revealed that it is possible to identify putative nested TEs by detecting these three types of patterns. The results were validated through BLAST alignments, which revealed the efficacy and usefulness of the new method, which is called Mamushka. PMID:27812277

  10. Non-peptidic analogs of the cell adhesion motif RGD prevent experimental liver injury.

    Science.gov (United States)

    Bruck, R; Hershkoviz, R; Lider, O; Shirin, H; Aeed, H; Halpern, Z

    2000-07-01

    In chronic viral hepatitis, autoimmune hepatitis, and some chronic cholestatic liver diseases, T lymphocytes serve as effector cells of the immunostimulatory processes. Cellular interactions of immune cells with extracellular matrix components are regulated primarily via the beta 1 subfamily of integrin receptors. The target epitope of several such integrin receptors is the Arg-Gly-Asp sequence, a cell adhesion motif shared by several matrix-associated adhesive glycoproteins. We review the use of synthetic non-peptidic analogs of RGD in the prevention of immune-mediated, concanavalin A-induced liver damage in mice and in inhibiting the development of liver cirrhosis in rats. The Con A-induced elevation of serum transaminases and tumor necrosis factor-alpha and the infiltration of liver tissue by inflammatory cells were inhibited by pretreatment of the mice with the synthetic RGD mimetics. In rats, the progression of thioacetamide-induced liver cirrhosis was markedly inhibited by the co-administration of the RGD mimetic SF-6,5. The compounds described here may be examined therapeutically for pathological conditions in the liver, manifested as necro-inflammation and fibrosis. PMID:10909422

  11. C/C++代码自动生成脚本语言接口的实现%Implementation of Automatic Generating Scripting Language Interfaces with C/C++ Code

    Institute of Scientific and Technical Information of China (English)

    官尚元; 张芝萍; 徐立锋; 缪敬

    2005-01-01

    对于开发灵活的科学软件来说,脚本语言是一个强大的工具.然而开发人员经常遇到一个问题:如何将编译过的C/C++代码集成到一个解释器.为了解决上述问题,设计了一个可扩展的编译器--接口产生器(IG).IG主要任务是把编译过的C/C++代码集成到脚本语言解释器中.因此,该文的主要目的就是解决上述相关问题.

  12. C/C++内存管理中静态区、栈和堆的相互关系%Study On static region、stack and heap in C/C++memory manage Via Assemble Language

    Institute of Scientific and Technical Information of China (English)

    火善栋; 杨旭东

    2013-01-01

      汇编语言是一门面向计算机硬件的符号化的机器语言,通过对汇编语言可以加深对计算机内部原理的理解。本文借助汇编语言低级化的特点,详细地分析了 C/C++内存管理中静态区、栈和堆的内在联系和区别。%The assemble Language is a signal machine lanquage of facing computer hardware,learning assemble Language can Catch on better inside principle of computer.This thesis make use of the characteristic of assemble Language and analusis in detail the relation and difference of static region、stack and heap in C/C++memory manage.

  13. New horizons for lipoprotein receptors

    DEFF Research Database (Denmark)

    Andersen, Olav M.; Dagil, Robert; Kragelund, Birthe Brandt

    2013-01-01

    , this dogma has transformed with the observation that β-propellers of some LRs actively engage in complex formation too. Based on an in-depth decomposition of current structures and sequences, we suggest that exploitation of the β-propellers as binding targets depends on receptor subgroups. In particular, we...... highlight the shutter mechanism of β-propellers as a general recognition motif for NxI-containing ligands, and we present indications that the generalized β-propeller-induced ligand release mechanism is not applicable for the larger LRs. For the giant LR members, we present evidence that their β-propellers...

  14. Functional characterization of transcription factor motifs using cross-species comparison across large evolutionary distances

    OpenAIRE

    Jaebum Kim; Ryan Cunningham; Brian James; Stefan Wyder; Gibson, Joshua D.; Oliver Niehuis; Zdobnov, Evgeny M.; Hugh M Robertson; Robinson, Gene E.; Werren, John H; Saurabh Sinha

    2010-01-01

    We address the problem of finding statistically significant associations between cis-regulatory motifs and functional gene sets, in order to understand the biological roles of transcription factors. We develop a computational framework for this task, whose features include a new statistical score for motif scanning, the use of different scores for predicting targets of different motifs, and new ways to deal with redundancies among significant motif-function associations. This framework is app...

  15. Selection against spurious promoter motifs correlates with translational efficiency across bacteria

    OpenAIRE

    Froula, Jeffrey L.; M. Pilar Francino

    2008-01-01

    Because binding of RNAP to misplaced sites could compromise the efficiency of transcription, natural selection for the optimization of gene expression should regulate the distribution of DNA motifs capable of RNAP-binding across the genome. Here we analyze the distribution of the -10 promoter motifs that bind the sigma(70) subunit of RNAP in 42 bacterial genomes. We show that selection on these motifs operates across the genome, maintaining an over-representation of -10 motifs in regulatory s...

  16. RNAMotifScanX: a graph alignment approach for RNA structural motif identification

    OpenAIRE

    Zhong, Cuncong; Zhang, Shaojie

    2015-01-01

    RNA structural motifs are recurrent three-dimensional (3D) components found in the RNA architecture. These RNA structural motifs play important structural or functional roles and usually exhibit highly conserved 3D geometries and base-interaction patterns. Analysis of the RNA 3D structures and elucidation of their molecular functions heavily rely on efficient and accurate identification of these motifs. However, efficient RNA structural motif search tools are lacking due to the high complexit...

  17. SPIC: A novel similarity metric for comparing transcription factor binding site motifs based on information contents

    OpenAIRE

    Zhang, Shaoqiang; Zhou, Xiguo; Du, Chuanbin; Su, Zhengchang

    2013-01-01

    Background Discovering transcription factor binding sites (TFBS) is one of primary challenges to decipher complex gene regulatory networks encrypted in a genome. A set of short DNA sequences identified by a transcription factor (TF) is known as a motif, which can be expressed accurately in matrix form such as a position-specific scoring matrix (PSSM) and a position frequency matrix. Very frequently, we need to query a motif in a database of motifs by seeking its similar motifs, merge similar ...

  18. Ubiquitous transgenic overexpression of C-C chemokine ligand 2: a model to assess the combined effect of high energy intake and continuous low-grade inflammation.

    Science.gov (United States)

    Rodríguez-Gallego, Esther; Riera-Borrull, Marta; Hernández-Aguilera, Anna; Mariné-Casadó, Roger; Rull, Anna; Beltrán-Debón, Raúl; Luciano-Mateo, Fedra; Menendez, Javier A; Vazquez-Martin, Alejandro; Sirvent, Juan J; Martín-Paredero, Vicente; Corbí, Angel L; Sierra-Filardi, Elena; Aragonès, Gerard; García-Heredia, Anabel; Camps, Jordi; Alonso-Villaverde, Carlos; Joven, Jorge

    2013-01-01

    Excessive energy management leads to low-grade, chronic inflammation, which is a significant factor predicting noncommunicable diseases. In turn, inflammation, oxidation, and metabolism are associated with the course of these diseases; mitochondrial dysfunction seems to be at the crossroads of mutual relationships. The migration of immune cells during inflammation is governed by the interaction between chemokines and chemokine receptors. Chemokines, especially C-C-chemokine ligand 2 (CCL2), have a variety of additional functions that are involved in the maintenance of normal metabolism. It is our hypothesis that a ubiquitous and continuous secretion of CCL2 may represent an animal model of low-grade chronic inflammation that, in the presence of an energy surplus, could help to ascertain the afore-mentioned relationships and/or to search for specific therapeutic approaches. Here, we present preliminary data on a mouse model created by using targeted gene knock-in technology to integrate an additional copy of the CCl2 gene in the Gt(ROSA)26Sor locus of the mouse genome via homologous recombination in embryonic stem cells. Short-term dietary manipulations were assessed and the findings include metabolic disturbances, premature death, and the manipulation of macrophage plasticity and autophagy. These results raise a number of mechanistic questions for future study.

  19. Ubiquitous Transgenic Overexpression of C-C Chemokine Ligand 2: A Model to Assess the Combined Effect of High Energy Intake and Continuous Low-Grade Inflammation

    Directory of Open Access Journals (Sweden)

    Esther Rodríguez-Gallego

    2013-01-01

    Full Text Available Excessive energy management leads to low-grade, chronic inflammation, which is a significant factor predicting noncommunicable diseases. In turn, inflammation, oxidation, and metabolism are associated with the course of these diseases; mitochondrial dysfunction seems to be at the crossroads of mutual relationships. The migration of immune cells during inflammation is governed by the interaction between chemokines and chemokine receptors. Chemokines, especially C-C-chemokine ligand 2 (CCL2, have a variety of additional functions that are involved in the maintenance of normal metabolism. It is our hypothesis that a ubiquitous and continuous secretion of CCL2 may represent an animal model of low-grade chronic inflammation that, in the presence of an energy surplus, could help to ascertain the afore-mentioned relationships and/or to search for specific therapeutic approaches. Here, we present preliminary data on a mouse model created by using targeted gene knock-in technology to integrate an additional copy of the CCl2 gene in the Gt(ROSA26Sor locus of the mouse genome via homologous recombination in embryonic stem cells. Short-term dietary manipulations were assessed and the findings include metabolic disturbances, premature death, and the manipulation of macrophage plasticity and autophagy. These results raise a number of mechanistic questions for future study.

  20. Proline primed helix length as a modulator of the nuclear receptor-coactivator interaction

    NARCIS (Netherlands)

    Fuchs, S.; Nguyen, H.D.; Phan, T.T.T.; Burton, M.F.; Nieto, L.; Vries-van Leeuwen, I.J. de; Schmidt, A.; Goodarzifard, M.; Agten, S.M.; Rose, R.; Ottmann, C.; Milroy, L.G.; Brunsveld, L.

    2013-01-01

    Nuclear receptor binding to coactivator proteins is an obligate first step in the regulation of gene transcription. Nuclear receptors preferentially bind to an LXXLL peptide motif which is highly conserved throughout the 300 or so natural coactivator proteins. This knowledge has shaped current under

  1. An angiotensin II type 1 receptor activation switch patch revealed through evolutionary trace analysis

    DEFF Research Database (Denmark)

    Bonde, Marie Mi; Yao, Rong; Ma, Jian-Nong;

    2010-01-01

    Seven transmembrane (7TM) or G protein-coupled receptors constitute a large superfamily of cell surface receptors sharing a structural motif of seven transmembrane spanning alpha helices. Their activation mechanism most likely involves concerted movements of the transmembrane helices, but remains...

  2. An Angiotensin II type 1 receptor activation switch patch revealed through Evolutionary Trace analysis

    DEFF Research Database (Denmark)

    Bonde, Marie Mi; Yao, Rong; Ma, Jian-Nong;

    2010-01-01

    Seven transmembrane (7TM) or G protein-coupled receptors constitute a large superfamily of cell surface receptors sharing a structural motif of seven transmembrane spanning alpha helices. Their activation mechanism most likely involves concerted movements of the transmembrane helices, but remains...

  3. A new motif for inhibitors of geranylgeranyl diphosphate synthase.

    Science.gov (United States)

    Foust, Benjamin J; Allen, Cheryl; Holstein, Sarah A; Wiemer, David F

    2016-08-15

    The enzyme geranylgeranyl diphosphate synthase (GGDPS) is believed to receive the substrate farnesyl diphosphate through one lipophilic channel and release the product geranylgeranyl diphosphate through another. Bisphosphonates with two isoprenoid chains positioned on the α-carbon have proven to be effective inhibitors of this enzyme. Now a new motif has been prepared with one isoprenoid chain on the α-carbon, a second included as a phosphonate ester, and the potential for a third at the α-carbon. The pivaloyloxymethyl prodrugs of several compounds based on this motif have been prepared and the resulting compounds have been tested for their ability to disrupt protein geranylgeranylation and induce cytotoxicity in myeloma cells. The initial biological studies reveal activity consistent with GGDPS inhibition, and demonstrate a structure-function relationship which is dependent on the nature of the alkyl group at the α-carbon. PMID:27338660

  4. SLIDER: A Generic Metaheuristic for the Discovery of Correlated Motifs in Protein-Protein Interaction Networks

    NARCIS (Netherlands)

    Boyen, P.; Dyck, van D.; Neven, F.; Ham, van R.C.H.J.; Dijk, van A.D.J.

    2011-01-01

    Correlated motif mining (CMM) is the problem of finding overrepresented pairs of patterns, called motifs, in sequences of interacting proteins. Algorithmic solutions for CMM thereby provide a computational method for predicting binding sites for protein interaction. In this paper, we adopt a motif-d

  5. Distinct configurations of protein complexes and biochemical pathways revealed by epistatic interaction network motifs

    LENUS (Irish Health Repository)

    Casey, Fergal

    2011-08-22

    Abstract Background Gene and protein interactions are commonly represented as networks, with the genes or proteins comprising the nodes and the relationship between them as edges. Motifs, or small local configurations of edges and nodes that arise repeatedly, can be used to simplify the interpretation of networks. Results We examined triplet motifs in a network of quantitative epistatic genetic relationships, and found a non-random distribution of particular motif classes. Individual motif classes were found to be associated with different functional properties, suggestive of an underlying biological significance. These associations were apparent not only for motif classes, but for individual positions within the motifs. As expected, NNN (all negative) motifs were strongly associated with previously reported genetic (i.e. synthetic lethal) interactions, while PPP (all positive) motifs were associated with protein complexes. The two other motif classes (NNP: a positive interaction spanned by two negative interactions, and NPP: a negative spanned by two positives) showed very distinct functional associations, with physical interactions dominating for the former but alternative enrichments, typical of biochemical pathways, dominating for the latter. Conclusion We present a model showing how NNP motifs can be used to recognize supportive relationships between protein complexes, while NPP motifs often identify opposing or regulatory behaviour between a gene and an associated pathway. The ability to use motifs to point toward underlying biological organizational themes is likely to be increasingly important as more extensive epistasis mapping projects in higher organisms begin.

  6. Graph animals, subgraph sampling, and motif search in large networks

    Science.gov (United States)

    Baskerville, Kim; Grassberger, Peter; Paczuski, Maya

    2007-09-01

    We generalize a sampling algorithm for lattice animals (connected clusters on a regular lattice) to a Monte Carlo algorithm for “graph animals,” i.e., connected subgraphs in arbitrary networks. As with the algorithm in [N. Kashtan , Bioinformatics 20, 1746 (2004)], it provides a weighted sample, but the computation of the weights is much faster (linear in the size of subgraphs, instead of superexponential). This allows subgraphs with up to ten or more nodes to be sampled with very high statistics, from arbitrarily large networks. Using this together with a heuristic algorithm for rapidly classifying isomorphic graphs, we present results for two protein interaction networks obtained using the tandem affinity purification (TAP) method: one of Escherichia coli with 230 nodes and 695 links, and one for yeast (Saccharomyces cerevisiae) with roughly ten times more nodes and links. We find in both cases that most connected subgraphs are strong motifs ( Z scores >10 ) or antimotifs ( Z scores motifs in E. coli being (nearly) bipartite graphs and having many pairs of nodes that connect to the same neighbors, while dominant motifs in yeast tend towards completeness or contain large cliques. We also explore a number of methods that do not rely on measurements of Z scores or comparisons with null models. For instance, we discuss the influence of specific complexes like the 26S proteasome in yeast, where a small number of complexes dominate the k cores with large k and have a decisive effect on the strongest motifs with 6-8 nodes. We also present Zipf plots of counts versus rank. They show broad distributions that are not power laws, in contrast to the case when disconnected subgraphs are included.

  7. The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

    OpenAIRE

    Kelwick, Richard; Desanlis, Ines; Wheeler, Grant N.; Edwards, Dylan R

    2015-01-01

    The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAM...

  8. Defense-Inducing Volatiles: In Search of the Active Motif

    OpenAIRE

    Heil, Martin; Lion, Ulrich; Boland, Wilhelm

    2008-01-01

    Herbivore-induced volatile organic compounds (VOCs) are widely appreciated as an indirect defense mechanism since carnivorous arthropods use VOCs as cues for host localization and then attack herbivores. Another function of VOCs is plant–plant signaling. That VOCs elicit defensive responses in neighboring plants has been reported from various species, and different compounds have been found to be active. In order to search for a structural motif that characterizes active VOCs, we used lima be...

  9. A motif-independent metric for DNA sequence specificity

    OpenAIRE

    Pinello Luca; Lo Bosco Giosuè; Hanlon Bret; Yuan Guo-Cheng

    2011-01-01

    Abstract Background Genome-wide mapping of protein-DNA interactions has been widely used to investigate biological functions of the genome. An important question is to what extent such interactions are regulated at the DNA sequence level. However, current investigation is hampered by the lack of computational methods for systematic evaluating sequence specificity. Results We present a simple, unbiased quantitative measure for DNA sequence specificity called the Motif Independent Measure (MIM)...

  10. Tricksters Trot to America: Areal Distribution of Folklore Motifs

    OpenAIRE

    Yuri Berezkin

    2010-01-01

    The folklore Trickster is usually considered a universally known combination of features intrinsic to human nature. However, there are strong anomalies in the areal distribution of such a figure. Sub-Saharan Africa, North America (except for the Arctic), Northeast Asia and South American Chaco not only are the preferred zones of tricksters’ activity but also share some peculiar trickster motifs unknown in most of the other regions. The range of animals which play the role of tricksters is als...

  11. Mouse mutants for the nicotinic acetylcholine receptor ß2 subunit display changes in cell adhesion and neurodegeneration response genes.

    Directory of Open Access Journals (Sweden)

    Carol M Rubin

    Full Text Available Mice lacking expression of the ß2 subunit of the neuronal nicotinic acetylcholine receptor (CHRNB2 display abnormal retinal waves and a dispersed projection of retinal ganglion cell (RGC axons to their dorsal lateral geniculate nuclei (dLGNs. Transcriptomes of LGN tissue from two independently generated Chrnb2-/- mutants and from wildtype mice were obtained at postnatal day 4 (P4, during the normal period of segregation of eye-specific afferents to the LGN. Microarray analysis reveals reduced expression of genes located on the cell membrane or in extracellular space, and of genes active in cell adhesion and calcium signaling. In particular, mRNA for cadherin 1 (Cdh1, a known axon growth regulator, is reduced to nearly undetectable levels in the LGN of P4 mutant mice and Lypd2 mRNA is similarly suppressed. Similar analysis of retinal tissue shows increased expression of crumbs 1 (Crb1 and chemokine (C-C motif ligand 21 (Ccl21 mRNAs in Chrnb2-/- mutant animals. Mutations in these genes are associated with retinal neuronal degeneration. The retinas of Chrnb2-/- mutants are normal in appearance, but the increased expression of these genes may also be involved in the abnormal projection patterns of RGC to the LGN. These data may provide the tools to distinguish the interplay between neural activity and molecular expression. Finally, comparison of the transcriptomes of the two different Chrnb2-/- mutant strains reveals the effects of genetic background upon gene expression.

  12. Event Networks and the Identification of Crime Pattern Motifs.

    Directory of Open Access Journals (Sweden)

    Toby Davies

    Full Text Available In this paper we demonstrate the use of network analysis to characterise patterns of clustering in spatio-temporal events. Such clustering is of both theoretical and practical importance in the study of crime, and forms the basis for a number of preventative strategies. However, existing analytical methods show only that clustering is present in data, while offering little insight into the nature of the patterns present. Here, we show how the classification of pairs of events as close in space and time can be used to define a network, thereby generalising previous approaches. The application of graph-theoretic techniques to these networks can then offer significantly deeper insight into the structure of the data than previously possible. In particular, we focus on the identification of network motifs, which have clear interpretation in terms of spatio-temporal behaviour. Statistical analysis is complicated by the nature of the underlying data, and we provide a method by which appropriate randomised graphs can be generated. Two datasets are used as case studies: maritime piracy at the global scale, and residential burglary in an urban area. In both cases, the same significant 3-vertex motif is found; this result suggests that incidents tend to occur not just in pairs, but in fact in larger groups within a restricted spatio-temporal domain. In the 4-vertex case, different motifs are found to be significant in each case, suggesting that this technique is capable of discriminating between clustering patterns at a finer granularity than previously possible.

  13. MAR characteristic motifs mediate episomal vector in CHO cells.

    Science.gov (United States)

    Lin, Yan; Li, Zhaoxi; Wang, Tianyun; Wang, Xiaoyin; Wang, Li; Dong, Weihua; Jing, Changqin; Yang, Xianjun

    2015-04-01

    An ideal gene therapy vector should enable persistent transgene expression without limitations in safety and reproducibility. Recent researches' insight into the ability of chromosomal matrix attachment regions (MARs) to mediate episomal maintenance of genetic elements allowed the development of a circular episomal vector. Although a MAR-mediated engineered vector has been developed, little is known on which motifs of MAR confer this function during interaction with the host genome. Here, we report an artificially synthesized DNA fragment containing only characteristic motif sequences that served as an alternative to human beta-interferon matrix attachment region sequence. The potential of the vector to mediate gene transfer in CHO cells was investigated. The short synthetic MAR motifs were found to mediate episomal vector at a low copy number for many generations without integration into the host genome. Higher transgene expression was maintained for at least 4 months. In addition, MAR was maintained episomally and conferred sustained EGFP expression even in nonselective CHO cells. All the results demonstrated that MAR characteristic sequence-based vector can function as stable episomes in CHO cells, supporting long-term and effective transgene expression.

  14. Motif structure and cooperation in real-world complex networks

    Science.gov (United States)

    Salehi, Mostafa; Rabiee, Hamid R.; Jalili, Mahdi

    2010-12-01

    Networks of dynamical nodes serve as generic models for real-world systems in many branches of science ranging from mathematics to physics, technology, sociology and biology. Collective behavior of agents interacting over complex networks is important in many applications. The cooperation between selfish individuals is one of the most interesting collective phenomena. In this paper we address the interplay between the motifs’ cooperation properties and their abundance in a number of real-world networks including yeast protein-protein interaction, human brain, protein structure, email communication, dolphins’ social interaction, Zachary karate club and Net-science coauthorship networks. First, the amount of cooperativity for all possible undirected subgraphs with three to six nodes is calculated. To this end, the evolutionary dynamics of the Prisoner’s Dilemma game is considered and the cooperativity of each subgraph is calculated as the percentage of cooperating agents at the end of the simulation time. Then, the three- to six-node motifs are extracted for each network. The significance of the abundance of a motif, represented by a Z-value, is obtained by comparing them with some properly randomized versions of the original network. We found that there is always a group of motifs showing a significant inverse correlation between their cooperativity amount and Z-value, i.e. the more the Z-value the less the amount of cooperativity. This suggests that networks composed of well-structured units do not have good cooperativity properties.

  15. Insertion of tetracysteine motifs into dopamine transporter extracellular domains.

    Directory of Open Access Journals (Sweden)

    Deanna M Navaroli

    Full Text Available The neuronal dopamine transporter (DAT is a major determinant of extracellular dopamine (DA levels and is the primary target for a variety of addictive and therapeutic psychoactive drugs. DAT is acutely regulated by protein kinase C (PKC activation and amphetamine exposure, both of which modulate DAT surface expression by endocytic trafficking. In order to use live imaging approaches to study DAT endocytosis, methods are needed to exclusively label the DAT surface pool. The use of membrane impermeant, sulfonated biarsenic dyes holds potential as one such approach, and requires introduction of an extracellular tetracysteine motif (tetraCys; CCPGCC to facilitate dye binding. In the current study, we took advantage of intrinsic proline-glycine (Pro-Gly dipeptides encoded in predicted DAT extracellular domains to introduce tetraCys motifs into DAT extracellular loops 2, 3, and 4. [(3H]DA uptake studies, surface biotinylation and fluorescence microscopy in PC12 cells indicate that tetraCys insertion into the DAT second extracellular loop results in a functional transporter that maintains PKC-mediated downregulation. Introduction of tetraCys into extracellular loops 3 and 4 yielded DATs with severely compromised function that failed to mature and traffic to the cell surface. This is the first demonstration of successful introduction of a tetracysteine motif into a DAT extracellular domain, and may hold promise for use of biarsenic dyes in live DAT imaging studies.

  16. Interlinking motifs and entropy landscapes of statistically interacting particles

    Directory of Open Access Journals (Sweden)

    P. Lu

    2012-03-01

    Full Text Available The s=1/2 Ising chain with uniform nearest-neighbor and next-nearest-neighbor coupling is used to construct a system of floating particles characterized by motifs of up to six consecutive local spins. The spin couplings cause the assembly of particles which, in turn, remain free of interaction energies even at high density. All microstates are configurations of particles from one of three different sets, excited from pseudo-vacua associated with ground states of periodicities one, two, and four. The motifs of particles and elements of pseudo-vacuum interlink in two shared site variables. The statistical interaction between particles is encoded in a generalized Pauli principle, describing how the placement of one particle modifies the options for placing further particles. In the statistical mechanical analysis arbitrary energies can be assigned to all particle species. The entropy is a function of the particle populations. The statistical interaction specifications are transparently built into that expression. The energies and structures of the particles alone govern the ordering at low temperature. Under special circumstances the particles can be replaced by more fundamental particles with shorter motifs that interlink in only one shared site variable. Structures emerge from interactions on two levels: particles with shapes from coupled spins and long-range ordering tendencies from statistically interacting particles with shapes.

  17. TOPDOM: database of conservatively located domains and motifs in proteins

    Science.gov (United States)

    Varga, Julia; Dobson, László; Tusnády, Gábor E.

    2016-01-01

    Summary: The TOPDOM database—originally created as a collection of domains and motifs located consistently on the same side of the membranes in α-helical transmembrane proteins—has been updated and extended by taking into consideration consistently localized domains and motifs in globular proteins, too. By taking advantage of the recently developed CCTOP algorithm to determine the type of a protein and predict topology in case of transmembrane proteins, and by applying a thorough search for domains and motifs as well as utilizing the most up-to-date version of all source databases, we managed to reach a 6-fold increase in the size of the whole database and a 2-fold increase in the number of transmembrane proteins. Availability and implementation: TOPDOM database is available at http://topdom.enzim.hu. The webpage utilizes the common Apache, PHP5 and MySQL software to provide the user interface for accessing and searching the database. The database itself is generated on a high performance computer. Contact: tusnady.gabor@ttk.mta.hu. Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27153630

  18. A Monte Carlo-based framework enhances the discovery and interpretation of regulatory sequence motifs

    Directory of Open Access Journals (Sweden)

    Seitzer Phillip

    2012-11-01

    Full Text Available Abstract Background Discovery of functionally significant short, statistically overrepresented subsequence patterns (motifs in a set of sequences is a challenging problem in bioinformatics. Oftentimes, not all sequences in the set contain a motif. These non-motif-containing sequences complicate the algorithmic discovery of motifs. Filtering the non-motif-containing sequences from the larger set of sequences while simultaneously determining the identity of the motif is, therefore, desirable and a non-trivial problem in motif discovery research. Results We describe MotifCatcher, a framework that extends the sensitivity of existing motif-finding tools by employing random sampling to effectively remove non-motif-containing sequences from the motif search. We developed two implementations of our algorithm; each built around a commonly used motif-finding tool, and applied our algorithm to three diverse chromatin immunoprecipitation (ChIP data sets. In each case, the motif finder with the MotifCatcher extension demonstrated improved sensitivity over the motif finder alone. Our approach organizes candidate functionally significant discovered motifs into a tree, which allowed us to make additional insights. In all cases, we were able to support our findings with experimental work from the literature. Conclusions Our framework demonstrates that additional processing at the sequence entry level can significantly improve the performance of existing motif-finding tools. For each biological data set tested, we were able to propose novel biological hypotheses supported by experimental work from the literature. Specifically, in Escherichia coli, we suggested binding site motifs for 6 non-traditional LexA protein binding sites; in Saccharomyces cerevisiae, we hypothesize 2 disparate mechanisms for novel binding sites of the Cse4p protein; and in Halobacterium sp. NRC-1, we discoverd subtle differences in a general transcription factor (GTF binding site motif

  19. Predicting the Dielectric Strength of c-C4F8 and SF6 Gas Mixtures by Monte Carlo Method

    Institute of Scientific and Technical Information of China (English)

    WU Bian-tao; XIAO Deng-ming

    2007-01-01

    An improved Monte Carlo method was used to simulate the motion of electrons in c-C4F8 and SF6 gas mixtures for pulsed townsend discharge. The electron swarm parameters such as effective ionization coefficient, (-α) and drift velocity over the E/N range from 280~700 Td(1Td= 10-21 V·m2) were calculated by employing a set of cross sections available in literature. From the variation cure of (-α) with SF6 partial pressure p, the limiting field (E/N)lim of gas mixture at different gas content was determined. It is found that the limiting field of c-C4F8 and SF6gas mixture is higher than that of pure SF6 at any SF6 mixture ratio. Simulation results show excellent agreement with experiment data available in previous literature.

  20. 将Python嵌入到C/C++应用程序中的编程方法

    Institute of Scientific and Technical Information of China (English)

    何炯

    2002-01-01

    Python是一种面向对象的语言.本文介绍了怎样在不同的层次上将Python编译器作为一种扩展语言嵌入到用C/C++编写的应用程序之中.嵌入了Python的C/C++应用程序可以完成某些Python特有的功能.文章也讲述了如何扩展嵌入的Python使其获得应用程序本身的功能.最后,讲述了怎样使链接到静态库的应用程序获得动态扩展.

  1. Ruthenium-Catalyzed Transfer Hydrogenation for C-C Bond Formation: Hydrohydroxyalkylation and Hydroaminoalkylation via Reactant Redox Pairs.

    Science.gov (United States)

    Perez, Felix; Oda, Susumu; Geary, Laina M; Krische, Michael J

    2016-06-01

    Merging the chemistry of transfer hydrogenation and carbonyl or imine addition, a broad new family of redox-neutral or reductive hydrohydroxyalkylations and hydroaminomethylations have been developed. In these processes, hydrogen redistribution between alcohols and π-unsaturated reactants is accompanied by C-C bond formation, enabling direct conversion of lower alcohols to higher alcohols. Similarly, hydrogen redistribution between amines to π-unsaturated reactants results in direct conversion of lower amines to higher amines. Alternatively, equivalent products of hydrohydroxyalkylation and hydroaminomethylation may be generated through the reaction of carbonyl compounds or imines with π-unsaturated reactants under the conditions of 2-propanol-mediated reductive coupling. Finally, using vicinally dioxygenated reactants, that is, diol, ketols, or diones, successive transfer hydrogenative coupling occurs to generate 2 C-C bonds, resulting in products of formal [4+2] cycloaddition. PMID:27573275

  2. Transfer Hydrogenation of C= C Double Bonds Catalyzed by Ruthenium Amido-Complexes:Scopes, Limitation and Enantioselectivity

    Institute of Scientific and Technical Information of China (English)

    XUE,Dong; CHENG,Ying-Chun; CUI,Xin; WANG,Qi-Wei; ZHU,Jin; DENG,Jin-Gen

    2004-01-01

    @@ The reduction of C = C double bonds is one of the most fundamental synthetic transformations and plays a key role in the manufacturing of a wide variety of bulk and fine chemicals. Hydrogenation of olefinic substrates can be achieved readily with molecular hydrogen in many cases, but transfer hydrogenation methods using suitable donor molecules such as formic acid or alcohols are receiving increasing attention as possible synthetic alternatives because it requires no special equipment and avoids the handling of potentially hazardous gaseous hydrogen.

  3. Application of Sol Self-Clean Bonded Al2O3-SiC-C Castable for Iron Runner

    Institute of Scientific and Technical Information of China (English)

    XU Guotao; ZHANG Honglei; CHEN Huasheng; WANG Yue; LI Huaiyuan; XIONG Yafei

    2006-01-01

    The properties and microstructure of sol self-clean bonded Al2O3-SiC-C castable in iron runner were studied, and the relation between the amount of sol selfclean binder and the properties of castable were discussed. It is believed that the addition of sol self-clean binder can improve the compressive strength, but has little effect on the bulk density and the apparent porosity,which enable the castable to be applicable in different conditions.

  4. Investigation of biopolymer-based hydrogels as green and heterogeneous catalysts in C-C bond formation

    OpenAIRE

    Kühbeck, Dennis

    2015-01-01

    The present dissertation evaluates the efficacy of different polysaccharides (e.g. chitosan, alginate and kappa-carrageenan) and proteins (e.g. gelatin, collagen, silk fibroin) as possible catalysts for a variety of C-C bond formation reactions. These biopolymers can be obtained in different forms (e.g. hydrogels, mesoporous materials). Among different forms hydrogels are one of the most interesting since they could act as biphasic and heterogeneous systems in chemical transformations and fa...

  5. First observation of the isospin violating decay J/psi -> Lambda(Sigma)over-bar(0) + c.c.

    NARCIS (Netherlands)

    Ablikim, M.; Achasov, M. N.; Ambrose, D. J.; An, F. F.; An, Q.; An, Z. H.; Bai, J. Z.; Ban, Y.; Becker, J.; Berger, N.; Bertani, M.; Bian, J. M.; Boger, E.; Bondarenko, O.; Boyko, I.; Briere, R. A.; Bytev, V.; Cai, X.; Cakir, O.; Calcaterra, A.; Cao, G. F.; Cetin, S. A.; Chang, J. F.; Chelkov, G.; Chen, G.; Chen, H. S.; Chen, J. C.; Chen, M. L.; Chen, S. J.; Chen, Y.; Chen, Y. B.; Cheng, H. P.; Chu, Y. P.; Cronin-Hennessy, D.; Dai, H. L.; Dai, J. P.; Dedovich, D.; Deng, Z. Y.; Denig, A.; Denysenko, I.; Destefanis, M.; Ding, W. M.; Ding, Y.; Dong, L. Y.; Dong, M. Y.; Du, S. X.; Fang, J.; Fang, S. S.; Fava, L.; Feldbauer, F.; Feng, C. Q.; Ferroli, R. B.; Fu, C. D.; Fu, J. L.; Gao, Y.; Geng, C.; Goetzen, K.; Gong, W. X.; Gradl, W.; Greco, M.; Gu, M. H.; Gu, Y. T.; Guan, Y. H.; Guo, A. Q.; Guo, L. B.; Guo, Y. P.; Han, Y. L.; Hao, X. Q.; Harris, F. A.; He, K. L.; He, M.; He, Z. Y.; Held, T.; Heng, Y. K.; Hou, Z. L.; Hu, H. M.; Hu, J. F.; Hu, T.; Huang, B.; Huang, G. M.; Huang, J. S.; Huang, X. T.; Huang, Y. P.; Hussain, T.; Ji, C. S.; Ji, Q.; Ji, X. B.; Ji, X. L.; Jia, L. K.; Jiang, L. L.; Jiang, X. S.; Jiao, J. B.; Jiao, Z.; Jin, D. P.; Jin, S.; Jing, F. F.; Kalantar-Nayestanaki, N.; Kavatsyuk, M.; Kuehn, W.; Lai, W.; Lange, J. S.; Li, C. H.; Li, Cheng; Li, Cui; Li, D. M.; Li, F.; Li, G.; Li, H. B.; Li, J. C.; Li, K.; Li, Lei; Li, N. B.; Li, Q. J.; Li, S. L.; Li, W. D.; Li, W. G.; Li, X. L.; Li, X. N.; Li, X. Q.; Li, X. R.; Li, Z. B.; Liang, H.; Liang, Y. F.; Liang, Y. T.; Liao, G. R.; Liao, X. T.; Liu, B. J.; Liu, C. L.; Liu, C. X.; Liu, C. Y.; Liu, F. H.; Liu, Fang; Liu, Feng; Liu, H.; Liu, H. B.; Liu, H. H.; Liu, H. M.; Liu, H. W.; Liu, J. P.; Liu, K. Y.; Liu, Kai; Liu, Kun; Liu, P. L.; Liu, S. B.; Liu, X.; Liu, X. H.; Liu, Y.; Liu, Y. B.; Liu, Z. A.; Liu, Zhiqiang; Liu, Zhiqing; Loehner, H.; Lu, G. R.; Lu, H. J.; Lu, J. G.; Lu, Q. W.; Lu, X. R.; Lu, Y. P.; Luo, C. L.; Luo, M. X.; Luo, T.; Luo, X. L.; Lv, M.; Ma, C. L.; Ma, F. C.; Ma, H. L.; Ma, Q. M.; Ma, S.; Ma, T.; Ma, X. Y.; Ma, Y.; Maas, F. E.; Maggiora, M.; Malik, Q. A.; Mao, H.; Mao, Y. J.; Mao, Z. P.; Messchendorp, J. G.; Min, J.; Min, T. J.; Mitchell, R. E.; Mo, X. H.; Morales, C. Morales; Motzko, C.; Muchnoi, N. Yu.; Muramatsu, H.; Nefedov, Y.; Nicholson, C.; Nikolaev, I. B.; Ning, Z.; Olsen, S. L.; Ouyang, Q.; Pacetti, S.; Park, J. W.; Pelizaeus, M.; Peng, H. P.; Peters, K.; Ping, J. L.; Ping, R. G.; Poling, R.; Prencipe, E.; Qi, M.; Qian, S.; Qiao, C. F.; Qin, X. S.; Qin, Y.; Qin, Z. H.; Qiu, J. F.; Rashid, K. H.; Rong, G.; Ruan, X. D.; Sarantsev, A.; Schaefer, B. D.; Schulze, J.; Shao, M.; Shen, C. P.; Shen, X. Y.; Sheng, H. Y.; Shepherd, M. R.; Song, X. Y.; Spataro, S.; Spruck, B.; Sun, D. H.; Sun, G. X.; Sun, J. F.; Sun, S. S.; Sun, X. D.; Sun, Y. J.; Sun, Y. Z.; Sun, Z. J.; Sun, Z. T.; Tang, C. J.; Tang, X.; Tang, X. F.; Tapan, I.; Thorndike, E. H.; Tian, H. L.; Toth, D.; Ullrich, M.; Varner, G. S.; Wang, B.; Wang, B. Q.; Wang, K.; Wang, L. L.; Wang, L. S.; Wang, M.; Wang, P.; Wang, P. L.; Wang, Q.; Wang, Q. J.; Wang, S. G.; Wang, X. L.; Wang, Y. D.; Wang, Y. F.; Wang, Y. Q.; Wang, Z.; Wang, Z. G.; Wang, Z. Y.; Wei, D. H.; Weidenkaff, P.; Wen, Q. G.; Wen, S. P.; Werner, M.; Wiedner, U.; Wu, L. H.; Wu, N.; Wu, S. X.; Wu, W.; Wu, Z.; Xia, L. G.; Xiao, Z. J.; Xie, Y. G.; Xiu, Q. L.; Xu, G. F.; Xu, G. M.; Xu, H.; Xu, Q. J.; Xu, X. P.; Xu, Z. R.; Xue, F.; Xue, Z.; Yan, L.; Yan, W. B.; Yan, Y. H.; Yang, H. X.; Yang, Y.; Yang, Y. X.; Ye, H.; Ye, M.; Ye, M. H.; Yu, B. X.; Yu, C. X.; Yu, J. S.; Yu, S. P.; Yuan, C. Z.; Yuan, W. L.; Yuan, Y.; Zafar, A. A.; Zallo, A.; Zeng, Y.; Zhang, B. X.; Zhang, B. Y.; Zhang, C. C.; Zhang, D. H.; Zhang, H. H.; Zhang, H. Y.; Zhang, J.; Zhang, J. Q.; Zhang, J. W.; Zhang, J. Y.; Zhang, J. Z.; Zhang, S. H.; Zhang, T. R.; Zhang, X. J.; Zhang, X. Y.; Zhang, Y.; Zhang, Y. H.; Zhang, Y. S.; Zhang, Z. P.; Zhang, Z. Y.; Zhao, G.; Zhao, H. S.; Zhao, J. W.; Zhao, K. X.; Zhao, Lei; Zhao, Ling; Zhao, M. G.; Zhao, Q.; Zhao, S. J.; Zhao, T. C.; Zhao, X. H.; Zhao, Y. B.; Zhao, Z. G.; Zhemchugov, A.; Zheng, B.; Zheng, J. P.; Zheng, Y. H.; Zheng, Z. P.; Zhong, B.; Zhong, J.; Zhou, L.; Zhou, X. K.; Zhou, X. R.; Zhu, C.; Zhu, K.; Zhu, K. J.; Zhu, S. H.; Zhu, X. L.; Zhu, X. W.; Zhu, Y. C.; Zhu, Y. M.; Zhu, Y. S.; Zhu, Z. A.; Zhuang, J.; Zou, B. S.; Zou, J. H.; Zuo, J. X.

    2012-01-01

    Using a sample of (225.2 +/- 2.8) x 10(6) J/psi events collected with the BESIII detector, we present results of a study of J/psi -> gamma Lambda(Lambda) over bar and report the first observation of the isospin violating decay J/psi -> Lambda(Sigma) over bar (0) + c.c., in which (Sigma) over bar (0)

  6. The solidification process of the AK12/SiC+C composite suspension in various heat exchange conditions

    OpenAIRE

    A. Dolata-Grosz; M. Dyzia; J. Śleziona

    2008-01-01

    Purpose: In the research work the result of the structure and solidification analysis for aluminium cast compositewith ceramic particles in different solidification conditions have been presented. The results of research on thesolidification process for heterophase composite have been shown.Design/methodology/approach: The solidification process of the AK12/SiC+C composite suspension invarious heat abstraction conditions was recorded using the ThermaCAMTME25 photometer system for temperaturec...

  7. Identification of G protein-coupled receptors for Drosophila PRXamide peptides, CCAP, corazonin, and AKH supports a theory of ligand-receptor coevolution

    OpenAIRE

    Park, Yoonseong; KIM, YOUNG-JOON; Adams, Michael E.

    2002-01-01

    G-protein coupled receptors (GPCRs) are ancient, ubiquitous sensors vital to environmental and physiological signaling throughout organismal life. With the publication of the Drosophila genome, numerous “orphan” GPCRs have become available for functional analysis. Here we characterize two groups of GPCRs predicted as receptors for peptides with a C-terminal amino acid sequence motif consisting of −PRXamide (PRXa). Assuming ligand-receptor coevolution, two alternative hypotheses were construct...

  8. Chemokine CCL2 and its receptor CCR2 in the medullary dorsal horn are involved in trigeminal neuropathic pain

    Directory of Open Access Journals (Sweden)

    Zhang Zhi-Jun

    2012-07-01

    Full Text Available Abstract Background Neuropathic pain in the trigeminal system is frequently observed in clinic, but the mechanisms involved are largely unknown. In addition, the function of immune cells and related chemicals in the mechanism of pain has been recognized, whereas few studies have addressed the potential role of chemokines in the trigeminal system in chronic pain. The present study was undertaken to test the hypothesis that chemokine C-C motif ligand 2 (CCL2-chemokine C-C motif receptor 2 (CCR2 signaling in the trigeminal nucleus is involved in the maintenance of trigeminal neuropathic pain. Methods The inferior alveolar nerve and mental nerve transection (IAMNT was used to induce trigeminal neuropathic pain. The expression of ATF3, CCL2, glial fibrillary acidic protein (GFAP, and CCR2 were detected by immunofluorescence histochemical staining and western blot. The cellular localization of CCL2 and CCR2 were examined by immunofluorescence double staining. The effect of a selective CCR2 antagonist, RS504393 on pain hypersensitivity was checked by behavioral testing. Results IAMNT induced persistent (>21 days heat hyperalgesia of the orofacial region and ATF3 expression in the mandibular division of the trigeminal ganglion. Meanwhile, CCL2 expression was increased in the medullary dorsal horn (MDH from 3 days to 21 days after IAMNT. The induced CCL2 was colocalized with astroglial marker GFAP, but not with neuronal marker NeuN or microglial marker OX-42. Astrocytes activation was also found in the MDH and it started at 3 days, peaked at 10 days and maintained at 21 days after IAMNT. In addition, CCR2 was upregulated by IAMNT in the ipsilateral medulla and lasted for more than 21 days. CCR2 was mainly colocalized with NeuN and few cells were colocalized with GFAP. Finally, intracisternal injection of CCR2 antagonist, RS504393 (1, 10 μg significantly attenuated IAMNT-induced heat hyperalgesia. Conclusion The data suggest that CCL2-CCR

  9. A method of quantitative characterization for the component of C/C composites based on the PLM video

    Science.gov (United States)

    Li, Y. X.; Qi, L. H.; Song, Y. S.; Li, H. J.

    2016-07-01

    PLM video is used for studying the microstructure of C/C composites, because it contains the structure and motion information at the same time. It means that PLM video could provide more comprehensive microstructure features of C/C composites, and then the microstructure could be quantitatively characterized by image processing. However, several unavoidable displacements still exist in the PLM video, which could occur during the process of image acquisition. Therefore, an image registration method was put forward to correct the displacements by the phase correlation, and further to achieve the quantitative characterization of component combined with image fusion and threshold segmentation based on the PLM video of C/C composites. Specifically, PLM video was decomposed to a frame sequence firstly. Then a series of processes was carried out on this basis, including selecting the frame as equal interval, segmenting the static and dynamic regions and correcting the relative displacements between the adjacent frames. Meanwhile, the result of image registration was verified through image fusion, and it indicates that the proposed method could eliminate the displacements effectively. Finally, some operations of image processing were used to segment the components and calculate their fractions, thus the quantitative calculation was achieved successfully.

  10. Leucine zipper motif in RRS1 is crucial for the regulation of Arabidopsis dual resistance protein complex RPS4/RRS1.

    Science.gov (United States)

    Narusaka, Mari; Toyoda, Kazuhiro; Shiraishi, Tomonori; Iuchi, Satoshi; Takano, Yoshitaka; Shirasu, Ken; Narusaka, Yoshihiro

    2016-01-11

    Arabidopsis thaliana leucine-rich repeat-containing (NLR) proteins RPS4 and RRS1, known as dual resistance proteins, confer resistance to multiple pathogen isolates, such as the bacterial pathogens Pseudomonas syringae and Ralstonia solanacearum and the fungal pathogen Colletotrichum higginsianum. RPS4 is a typical Toll/interleukin 1 Receptor (TIR)-type NLR, whereas RRS1 is an atypical TIR-NLR that contains a leucine zipper (LZ) motif and a C-terminal WRKY domain. RPS4 and RRS1 are localised near each other in a head-to-head orientation. In this study, direct mutagenesis of the C-terminal LZ motif in RRS1 caused an autoimmune response and stunting in the mutant. Co-immunoprecipitation analysis indicated that full-length RPS4 and RRS1 are physically associated with one another. Furthermore, virus-induced gene silencing experiments showed that hypersensitive-like cell death triggered by RPS4/LZ motif-mutated RRS1 depends on EDS1. In conclusion, we suggest that the RRS1-LZ motif is crucial for the regulation of the RPS4/RRS1 complex.

  11. A novel alignment-free method for comparing transcription factor binding site motifs.

    Directory of Open Access Journals (Sweden)

    Minli Xu

    Full Text Available BACKGROUND: Transcription factor binding site (TFBS motifs can be accurately represented by position frequency matrices (PFM or other equivalent forms. We often need to compare TFBS motifs using their PFMs in order to search for similar motifs in a motif database, or cluster motifs according to their binding preference. The majority of current methods for motif comparison involve a similarity metric for column-to-column comparison and a method to find the optimal position alignment between the two compared motifs. In some applications, alignment-free methods might be preferred; however, few such methods with high accuracy have been described. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a novel alignment-free method for quantifying the similarity of motifs using their PFMs by converting PFMs into k-mer vectors. The motifs could then be compared by measuring the similarity among their corresponding k-mer vectors. CONCLUSIONS/SIGNIFICANCE: We demonstrate that our method in general achieves similar performance or outperforms the existing methods for clustering motifs according to their binding preference and identifying similar motifs of transcription factors of the same family.

  12. A Novel Alignment-Free Method for Comparing Transcription Factor Binding Site Motifs

    Science.gov (United States)

    Xu, Minli; Su, Zhengchang

    2010-01-01

    Background Transcription factor binding site (TFBS) motifs can be accurately represented by position frequency matrices (PFM) or other equivalent forms. We often need to compare TFBS motifs using their PFMs in order to search for similar motifs in a motif database, or cluster motifs according to their binding preference. The majority of current methods for motif comparison involve a similarity metric for column-to-column comparison and a method to find the optimal position alignment between the two compared motifs. In some applications, alignment-free methods might be preferred; however, few such methods with high accuracy have been described. Methodology/Principal Findings Here we describe a novel alignment-free method for quantifying the similarity of motifs using their PFMs by converting PFMs into k-mer vectors. The motifs could then be compared by measuring the similarity among their corresponding k-mer vectors. Conclusions/Significance We demonstrate that our method in general achieves similar performance or outperforms the existing methods for clustering motifs according to their binding preference and identifying similar motifs of transcription factors of the same family. PMID:20098703

  13. Motif-based analysis of large nucleotide data sets using MEME-ChIP.

    Science.gov (United States)

    Ma, Wenxiu; Noble, William S; Bailey, Timothy L

    2014-01-01

    MEME-ChIP is a web-based tool for analyzing motifs in large DNA or RNA data sets. It can analyze peak regions identified by ChIP-seq, cross-linking sites identified by CLIP-seq and related assays, as well as sets of genomic regions selected using other criteria. MEME-ChIP performs de novo motif discovery, motif enrichment analysis, motif location analysis and motif clustering, providing a comprehensive picture of the DNA or RNA motifs that are enriched in the input sequences. MEME-ChIP performs two complementary types of de novo motif discovery: weight matrix-based discovery for high accuracy; and word-based discovery for high sensitivity. Motif enrichment analysis using DNA or RNA motifs from human, mouse, worm, fly and other model organisms provides even greater sensitivity. MEME-ChIP's interactive HTML output groups and aligns significant motifs to ease interpretation. This protocol takes less than 3 h, and it provides motif discovery approaches that are distinct and complementary to other online methods. PMID:24853928

  14. Defining the functional binding sites of interleukin 12 receptor β1 and interleukin 23 receptor to Janus kinases.

    Science.gov (United States)

    Floss, Doreen M; Klöcker, Tobias; Schröder, Jutta; Lamertz, Larissa; Mrotzek, Simone; Strobl, Birgit; Hermanns, Heike; Scheller, Jürgen

    2016-07-15

    The interleukin (IL)-12-type cytokines IL-12 and IL-23 are involved in T-helper (Th) 1 and Th17 immunity, respectively. They share the IL-12 receptor β1 (IL-12Rβ1) as one component of their receptor signaling complexes, with IL-12Rβ2 as second receptor for IL-12 and IL-23R for IL-23 signal transduction. Stimulation with IL-12 and IL-23 results in activation of receptor-associated Janus kinases (Jak) and phosphorylation of STAT proteins in target cells. The Janus kinase tyrosine kinase (Tyk) 2 associates with IL-12Rβ1, whereas Jak2 binds to IL-23R and also to IL-12Rβ2. Receptor association of Jak2 is mediated by Box1 and Box2 motifs located within the intracellular domain of the receptor chains. Here we define the Box1 and Box2 motifs in IL-12Rβ1 and an unusual Jak2-binding site in IL-23R by the use of deletion and site-directed mutagenesis. Our data show that nonfunctional box motifs abolish IL-12- and IL-23-induced STAT3 phosphorylation and cytokine-dependent proliferation of Ba/F3 cells. Coimmunoprecipitation of Tyk2 by IL-12Rβ1 and Jak2 by IL‑23R supported these findings. In addition, our data demonstrate that association of Jak2 with IL-23R is mandatory for IL-12 and/or IL-23 signaling, whereas Tyk2 seems to be dispensable.

  15. ITAM-coupled receptors inhibit IFNAR signaling and alter macrophage responses to TLR4 and Listeria monocytogenes1

    OpenAIRE

    Huynh, Linda; WANG, LU; Shi, Chao; Park-Min, Kyung-Hyun; Ivashkiv, Lionel B.

    2012-01-01

    Immunoreceptor tyrosine based activation motif (ITAM)-coupled receptors play an essential role in regulating macrophage activation and function by cross-regulating signaling from heterologous receptors. We investigated mechanisms by which ITAM-associated receptors inhibit type I interferon (IFN-α/β) signaling in primary human macrophages and tested the effects of simultaneous ligation of ITAM-associated receptors and TLR4 on TLR4-induced Jak-STAT signaling that is mediated by autocrine IFN-β....

  16. Discriminative motif discovery in DNA and protein sequences using the DEME algorithm

    Directory of Open Access Journals (Sweden)

    Bailey Timothy L

    2007-10-01

    Full Text Available Abstract Background Motif discovery aims to detect short, highly conserved patterns in a collection of unaligned DNA or protein sequences. Discriminative motif finding algorithms aim to increase the sensitivity and selectivity of motif discovery by utilizing a second set of sequences, and searching only for patterns that can differentiate the two sets of sequences. Potential applications of discriminative motif discovery include discovering transcription factor binding site motifs in ChIP-chip data and finding protein motifs involved in thermal stability using sets of orthologous proteins from thermophilic and mesophilic organisms. Results We describe DEME, a discriminative motif discovery algorithm for use with protein and DNA sequences. Input to DEME is two sets of sequences; a "positive" set and a "negative" set. DEME represents motifs using a probabilistic model, and uses a novel combination of global and local search to find the motif that optimally discriminates between the two sets of sequences. DEME is unique among discriminative motif finders in that it uses an informative Bayesian prior on protein motif columns, allowing it to incorporate prior knowledge of residue characteristics. We also introduce four, synthetic, discriminative motif discovery problems that are designed for evaluating discriminative motif finders in various biologically motivated contexts. We test DEME using these synthetic problems and on two biological problems: finding yeast transcription factor binding motifs in ChIP-chip data, and finding motifs that discriminate between groups of thermophilic and mesophilic orthologous proteins. Conclusion Using artificial data, we show that DEME is more effective than a non-discriminative approach when there are "decoy" motifs or when a variant of the motif is present in the "negative" sequences. With real data, we show that DEME is as good, but not better than non-discriminative algorithms at discovering yeast transcription

  17. Predicting Kinase Activity in Angiotensin Receptor Phosphoproteomes Based on Sequence-Motifs and Interactions

    DEFF Research Database (Denmark)

    Bøgebo, Rikke; Horn, Heiko; Olsen, Jesper V;

    2014-01-01

    -arrestin dependent signalling. Two complimentary global phosphoproteomics studies have analyzed the complex signalling induced by the AT1aR. Here we integrate the data sets from these studies and perform a joint analysis using a novel method for prediction of differential kinase activity from phosphoproteomics data...... developed a new method for kinase-centric analysis of phosphoproteomes to pinpoint differential kinase activity in large-scale data sets....

  18. DNA nanotechnology based on i-motif structures.

    Science.gov (United States)

    Dong, Yuanchen; Yang, Zhongqiang; Liu, Dongsheng

    2014-06-17

    CONSPECTUS: Most biological processes happen at the nanometer scale, and understanding the energy transformations and material transportation mechanisms within living organisms has proved challenging. To better understand the secrets of life, researchers have investigated artificial molecular motors and devices over the past decade because such systems can mimic certain biological processes. DNA nanotechnology based on i-motif structures is one system that has played an important role in these investigations. In this Account, we summarize recent advances in functional DNA nanotechnology based on i-motif structures. The i-motif is a DNA quadruplex that occurs as four stretches of cytosine repeat sequences form C·CH(+) base pairs, and their stabilization requires slightly acidic conditions. This unique property has produced the first DNA molecular motor driven by pH changes. The motor is reliable, and studies show that it is capable of millisecond running speeds, comparable to the speed of natural protein motors. With careful design, the output of these types of motors was combined to drive micrometer-sized cantilevers bend. Using established DNA nanostructure assembly and functionalization methods, researchers can easily integrate the motor within other DNA assembled structures and functional units, producing DNA molecular devices with new functions such as suprahydrophobic/suprahydrophilic smart surfaces that switch, intelligent nanopores triggered by pH changes, molecular logic gates, and DNA nanosprings. Recently, researchers have produced motors driven by light and electricity, which have allowed DNA motors to be integrated within silicon-based nanodevices. Moreover, some devices based on i-motif structures have proven useful for investigating processes within living cells. The pH-responsiveness of the i-motif structure also provides a way to control the stepwise assembly of DNA nanostructures. In addition, because of the stability of the i-motif, this

  19. DNA nanotechnology based on i-motif structures.

    Science.gov (United States)

    Dong, Yuanchen; Yang, Zhongqiang; Liu, Dongsheng

    2014-06-17

    CONSPECTUS: Most biological processes happen at the nanometer scale, and understanding the energy transformations and material transportation mechanisms within living organisms has proved challenging. To better understand the secrets of life, researchers have investigated artificial molecular motors and devices over the past decade because such systems can mimic certain biological processes. DNA nanotechnology based on i-motif structures is one system that has played an important role in these investigations. In this Account, we summarize recent advances in functional DNA nanotechnology based on i-motif structures. The i-motif is a DNA quadruplex that occurs as four stretches of cytosine repeat sequences form C·CH(+) base pairs, and their stabilization requires slightly acidic conditions. This unique property has produced the first DNA molecular motor driven by pH changes. The motor is reliable, and studies show that it is capable of millisecond running speeds, comparable to the speed of natural protein motors. With careful design, the output of these types of motors was combined to drive micrometer-sized cantilevers bend. Using established DNA nanostructure assembly and functionalization methods, researchers can easily integrate the motor within other DNA assembled structures and functional units, producing DNA molecular devices with new functions such as suprahydrophobic/suprahydrophilic smart surfaces that switch, intelligent nanopores triggered by pH changes, molecular logic gates, and DNA nanosprings. Recently, researchers have produced motors driven by light and electricity, which have allowed DNA motors to be integrated within silicon-based nanodevices. Moreover, some devices based on i-motif structures have proven useful for investigating processes within living cells. The pH-responsiveness of the i-motif structure also provides a way to control the stepwise assembly of DNA nanostructures. In addition, because of the stability of the i-motif, this

  20. Sequence-based classification using discriminatory motif feature selection.

    Directory of Open Access Journals (Sweden)

    Hao Xiong

    Full Text Available Most existing methods for sequence-based classification use exhaustive feature generation, employing, for example, all k-mer patterns. The motivation behind such (enumerative approaches is to minimize the potential for overlooking important features. However, there are shortcomings to this strategy. First, practical constraints limit the scope of exhaustive feature generation to patterns of length ≤ k, such that potentially important, longer (> k predictors are not considered. Second, features so generated exhibit strong dependencies, which can complicate understanding of derived classification rules. Third, and most importantly, numerous irrelevant features are created. These concerns can compromise prediction and interpretation. While remedies have been proposed, they tend to be problem-specific and not broadly applicable. Here, we develop a generally applicable methodology, and an attendant software pipeline, that is predicated on discriminatory motif finding. In addition to the traditional training and validation partitions, our framework entails a third level of data partitioning, a discovery partition. A discriminatory motif finder is used on sequences and associated class labels in the discovery partition to yield a (small set of features. These features are then used as inputs to a classifier in the training partition. Finally, performance assessment occurs on the validation partition. Important attributes of our approach are its modularity (any discriminatory motif finder and any classifier can be deployed and its universality (all data, including sequences that are unaligned and/or of unequal length, can be accommodated. We illustrate our approach on two nucleosome occupancy datasets and a protein solubility dataset, previously analyzed using enumerative feature generation. Our method achieves excellent performance results, with and without optimization of classifier tuning parameters. A Python pipeline implementing the approach is

  1. Identification of imine reductase-specific sequence motifs.

    Science.gov (United States)

    Fademrecht, Silvia; Scheller, Philipp N; Nestl, Bettina M; Hauer, Bernhard; Pleiss, Jürgen

    2016-05-01

    Chiral amines are valuable building blocks for the production of a variety of pharmaceuticals, agrochemicals and other specialty chemicals. Only recently, imine reductases (IREDs) were discovered which catalyze the stereoselective reduction of imines to chiral amines. Although several IREDs were biochemically characterized in the last few years, knowledge of the reaction mechanism and the molecular basis of substrate specificity and stereoselectivity is limited. To gain further insights into the sequence-function relationships, the Imine Reductase Engineering Database (www.IRED.BioCatNet.de) was established and a systematic analysis of 530 putative IREDs was performed. A standard numbering scheme based on R-IRED-Sk was introduced to facilitate the identification and communication of structurally equivalent positions in different proteins. A conservation analysis revealed a highly conserved cofactor binding region and a predominantly hydrophobic substrate binding cleft. Two IRED-specific motifs were identified, the cofactor binding motif GLGxMGx5 [ATS]x4 Gx4 [VIL]WNR[TS]x2 [KR] and the active site motif Gx[DE]x[GDA]x[APS]x3 {K}x[ASL]x[LMVIAG]. Our results indicate a preference toward NADPH for all IREDs and explain why, despite their sequence similarity to β-hydroxyacid dehydrogenases (β-HADs), no conversion of β-hydroxyacids has been observed. Superfamily-specific conservations were investigated to explore the molecular basis of their stereopreference. Based on our analysis and previous experimental results on IRED mutants, an exclusive role of standard position 187 for stereoselectivity is excluded. Alternatively, two standard positions 139 and 194 were identified which are superfamily-specifically conserved and differ in R- and S-selective enzymes. Proteins 2016; 84:600-610. © 2016 Wiley Periodicals, Inc. PMID:26857686

  2. Short sequence motifs, overrepresented in mammalian conservednon-coding sequences

    Energy Technology Data Exchange (ETDEWEB)

    Minovitsky, Simon; Stegmaier, Philip; Kel, Alexander; Kondrashov,Alexey S.; Dubchak, Inna

    2007-02-21

    Background: A substantial fraction of non-coding DNAsequences of multicellular eukaryotes is under selective constraint. Inparticular, ~;5 percent of the human genome consists of conservednon-coding sequences (CNSs). CNSs differ from other genomic sequences intheir nucleotide composition and must play important functional roles,which mostly remain obscure.Results: We investigated relative abundancesof short sequence motifs in all human CNSs present in the human/mousewhole-genome alignments vs. three background sets of sequences: (i)weakly conserved or unconserved non-coding sequences (non-CNSs); (ii)near-promoter sequences (located between nucleotides -500 and -1500,relative to a start of transcription); and (iii) random sequences withthe same nucleotide composition as that of CNSs. When compared tonon-CNSs and near-promoter sequences, CNSs possess an excess of AT-richmotifs, often containing runs of identical nucleotides. In contrast, whencompared to random sequences, CNSs contain an excess of GC-rich motifswhich, however, lack CpG dinucleotides. Thus, abundance of short sequencemotifs in human CNSs, taken as a whole, is mostly determined by theiroverall compositional properties and not by overrepresentation of anyspecific short motifs. These properties are: (i) high AT-content of CNSs,(ii) a tendency, probably due to context-dependent mutation, of A's andT's to clump, (iii) presence of short GC-rich regions, and (iv) avoidanceof CpG contexts, due to their hypermutability. Only a small number ofshort motifs, overrepresented in all human CNSs are similar to bindingsites of transcription factors from the FOX family.Conclusion: Human CNSsas a whole appear to be too broad a class of sequences to possess strongfootprints of any short sequence-specific functions. Such footprintsshould be studied at the level of functional subclasses of CNSs, such asthose which flank genes with a particular pattern of expression. Overallproperties of CNSs are affected by

  3. Tricksters Trot to America: Areal Distribution of Folklore Motifs

    Directory of Open Access Journals (Sweden)

    Yuri Berezkin

    2010-12-01

    Full Text Available The folklore Trickster is usually considered a universally known combination of features intrinsic to human nature. However, there are strong anomalies in the areal distribution of such a figure. Sub-Saharan Africa, North America (except for the Arctic, Northeast Asia and South American Chaco not only are the preferred zones of tricksters’ activity but also share some peculiar trickster motifs unknown in most of the other regions. The range of animals which play the role of tricksters is also restricted and not always easily explained, E.g. the Hare and Spider, known in both Africa and North America, are neither “mediators” between life and death (suggested by C. Lévi-Strauss for Coyote nor “really tricky” (“materialistic” hypothesis of M. Harris. The set of trickster motifs and the zoo- or anthropomorphic impersonations of the Trickster are independentvariables. The same episodes are easily linked to different tricksters while every trickster usually attracts episodes characteristic of a particular region. Though the original emergence of Trickster as a mental construct can indeed be rooted in human psychology (and where else?, the distribution of tricksters in folklore is discretionary and depends of many uncertain, i.e. chance, factors. The wide spread or lack of tricksters in certain cultural areas hardly reflect any fundamental differences in the psychology of inhabitants of these regions. The study of trickster motifs, just as of any other folklore motifs, helps us reconstruct possible historic links between populations. The African – North American links remain enigmatic (independent emergence is possible but slight historicallinks cannot be completely excluded but the parallels between (Western and Northeast Siberian – North American tricksters are almost certainly due to former cultural ties across Northern Asia. Another interesting case is the proliferation of tricksters with different zoomorphic and other identities

  4. Present status of quinoxaline motifs: excellent pathfinders in therapeutic medicine.

    Science.gov (United States)

    Ajani, Olayinka Oyewale

    2014-10-01

    Quinoxalines belong to a class of excellent heterocyclic scaffolds owing to their wide biological properties and diverse therapeutic applications in medicinal research. They are complementary in shapes and charges to numerous biomolecules they interact with, thereby resulting in increased binding affinity. The pharmacokinetic properties of drugs bearing quinoxaline cores have shown them to be relatively easy to administer either as intramuscular solutions, oral capsules or rectal suppositories. This work deals with recent advances in the synthesis and pharmacological diversities of quinoxaline motifs which might pave ways for novel drugs development.

  5. Nucleic Acid i-Motif Structures in Analytical Chemistry.

    Science.gov (United States)

    Alba, Joan Josep; Sadurní, Anna; Gargallo, Raimundo

    2016-09-01

    Under the appropriate experimental conditions of pH and temperature, cytosine-rich segments in DNA or RNA sequences may produce a characteristic folded structure known as an i-motif. Besides its potential role in vivo, which is still under investigation, this structure has attracted increasing interest in other fields due to its sharp, fast and reversible pH-driven conformational changes. This "on/off" switch at molecular level is being used in nanotechnology and analytical chemistry to develop nanomachines and sensors, respectively. This paper presents a review of the latest applications of this structure in the field of chemical analysis.

  6. Real Time Motif Classification from Database Using Intelligent Algorithms

    Directory of Open Access Journals (Sweden)

    Paresh Kotak

    2012-12-01

    Full Text Available The amount of raw data being accumulated in the databases is increasing at an inconceivable rate.However, these data-rich databases are poor in providing substantial information. This is where datamining comes into picture. Specifically, data mining is "the process of extracting or mining informationfrom large amount of data". Motif classification has been an active area of research in data mining. Itconsists of assigning a data instance to one of the predefined classes/groups based upon the knowledgegained from previously seen (classified data.

  7. Peroxisome proliferator-activated receptor {alpha} agonists modulate Th1 and Th2 chemokine secretion in normal thyrocytes and Graves' disease

    Energy Technology Data Exchange (ETDEWEB)

    Antonelli, Alessandro, E-mail: a.antonelli@med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Ferrari, Silvia Martina, E-mail: sm.ferrari@int.med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Frascerra, Silvia, E-mail: lafrasce@gmail.com [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Corrado, Alda, E-mail: dala_res@hotmail.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Pupilli, Cinzia, E-mail: c.pupilli@dfc.unifi.it [Endocrinology Unit, Azienda Ospedaliera Careggi and University of Florence, Viale Morgagni 85, I-50134, Florence (Italy); Bernini, Giampaolo, E-mail: g.bernini@int.med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Benvenga, Salvatore, E-mail: s.benvenga@me.nettuno.it [Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Messina, Piazza Pugliatti 1, I-98122, Messina (Italy); Ferrannini, Ele, E-mail: eferrannini@med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Fallahi, Poupak, E-mail: poupak@int.med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy)

    2011-07-01

    Until now, no data are present about the effect of peroxisome proliferator-activated receptor (PPAR){alpha} activation on the prototype Th1 [chemokine (C-X-C motif) ligand (CXCL)10] (CXCL10) and Th2 [chemokine (C-C motif) ligand 2] (CCL2) chemokines secretion in thyroid cells. The role of PPAR{alpha} and PPAR{gamma} activation on CXCL10 and CCL2 secretion was tested in Graves' disease (GD) and control primary thyrocytes stimulated with interferon (IFN){gamma} and tumor necrosis factor (TNF){alpha}. IFN{gamma} stimulated both CXCL10 and CCL2 secretion in primary GD and control thyrocytes. TNF{alpha} alone stimulated CCL2 secretion, while had no effect on CXCL10. The combination of IFN{gamma} and TNF{alpha} had a synergistic effect both on CXCL10 and CCL2 chemokines in GD thyrocytes at levels comparable to those of controls. PPAR{alpha} activators inhibited the secretion of both chemokines (stimulated with IFN{gamma} and TNF{alpha}) at a level higher (for CXCL10, about 60-72%) than PPAR{gamma} agonists (about 25-35%), which were confirmed to inhibit CXCL10, but not CCL2. Our data show that CCL2 is modulated by IFN{gamma} and TNF{alpha} in GD and normal thyrocytes. Furthermore we first show that PPAR{alpha} activators inhibit the secretion of CXCL10 and CCL2 in thyrocytes, suggesting that PPAR{alpha} may be involved in the modulation of the immune response in the thyroid.

  8. Characterization of the ligand-dependent transactivation domain of thyroid hormone receptor.

    OpenAIRE

    Barettino, D; Vivanco Ruiz, M M; Stunnenberg, H.G.

    1994-01-01

    Transcriptional activation by nuclear receptors is achieved through autonomous activation functions (AFs), a constitutive N-terminal AF-1 and a C-terminal, ligand-dependent AF-2 that comprises a motif conserved between nuclear receptors. We have performed an extensive mutational analysis of the putative AF-2 domain of chicken thyroid hormone receptor alpha (cT3R alpha). We show that the AF-2 region mediates transactivation as well as transcriptional interference (squelching), not only between...

  9. Effectiveness of Diffusion Barrier Coatings for Mo-Re Embedded in C/SiC and C/C

    Science.gov (United States)

    Glass, David E.; Shenoy, Ravi N.; Wang, Zeng-Mei; Halbig, Michael C.

    2001-01-01

    Advanced high-temperature cooling applications may often require the elevated-temperature capability of carbon/silicon carbide or carbon/carbon composites in combination with the hermetic capability of metallic tubes. In this paper, the effects of C/SiC and C/C on tubes fabricated from several different refractory metals were evaluated. Though Mo, Nb, and Re were evaluated in the present study, the primary effort was directed toward two alloys of Mo-Re, namely, arc cast Mo-41Re and powder metallurgy Mo-47.5Re. Samples of these refractory metals were subjected to either the PyC/SiC deposition or embedding in C/C. MoSi2(Ge), R512E, and TiB2 coatings were included on several of the samples as potential diffusion barriers. The effects of the processing and thermal exposure on the samples were evaluated by conducting burst tests, microhardness surveys, and scanning electron microscopic examination (using either secondary electron or back scattered electron imaging and energy dispersive spectroscopy). The results showed that a layer of brittle Mo-carbide formed on the substrates of both the uncoated Mo-41Re and the uncoated Mo-47.5Re, subsequent to the C/C or the PyC/SiC processing. Both the R512E and the MoSi2(Ge) coatings were effective in preventing not only the diffusion of C into the Mo-Re substrate, but also the formation of the Mo-carbides. However, none of the coatings were effective at preventing both C and Si diffusion without some degradation of the substrate.

  10. Method 446.0: In Vitro Determination of Chlorophylls a, b, c + c and Pheopigments in 1 2Marine And Freshwater Algae by Visible Spectrophotometry

    Science.gov (United States)

    This method provides a procedure for determination of chlorophylls a (chl a), b (chl b), c + c 1 2 (chl c + c ) and pheopigments of chlorophyll a (pheo a) 1 2 found in marine and freshwater phytoplankton. Chlorophyllide a is determined as chl a. Visible wavelength spectrophotomet...

  11. 基于C & C08-Q的UniCenter2013中间层的设计与实现%Design and implementation of UniCenter2013 intermediate layer based on C & C08-Q

    Institute of Scientific and Technical Information of China (English)

    李淑玲

    2014-01-01

    基于C&C08-Q的UniCenter2013呼叫中心项目,将强大的互联网同固定电话网统一起来,为客户提供了一个功能完备且全天候服务的客户中心。中间层是整个呼叫中心系统构建中的基础模块,本文为用户提供了一个完善的数据库访问解决方案,从而增强了系统的扩展性和可维护性。%The UniCenter2013 Call Center project is based on C&C08-Q,integrating powerful Internet and fixed telephone network,providing a feature complete and all whether service customer center.The intermediate layer is the basic module in the whole call center system, this chapter providing a perfect solution for accessing the database,so enhanced the system extensibility and maintainability.

  12. Palladium complexes containing diphosphine and sulfonated phosphine ligands for c-c bond forming reactions. catalytic and mechanistic studies

    OpenAIRE

    García Suárez, Eduardo José

    2007-01-01

    El uso de compuestos de paladio(II) para catalizar reacciones de copolimerización de monóxido de carbono y olefinas así como otros tipos de reacciones de formación de enlaces C-C muestra un creciente interés, prueba de ello es el importante numero de publicaciones realizadas en estos últimos años.En catálisis una de las mayores causas de baja productividad es la degradación del catalizador a especies menos activas. Por este motivo se dedican constantemente esfuerzos al diseño de ligandos capa...

  13. EFFECTS OF HIGH TEMPERATURE PRETREATMENTS ON HIGH TEMPERATURE FRACTURE BEHAVIOR OF SiC-C/SiC

    Institute of Scientific and Technical Information of China (English)

    X.G. Luan; L.F. Cheng; S.R. Qiao; J. Zhang

    2004-01-01

    The samples made from a SiC-C/SiC composite were pretreated in Ar under creep,fatigue, creep and fatigue interaction, as well as in dry oxygen and wet oxygen under fatigue at 1300℃ for 15 hours. The fracture behaviors of the pretreated samples were investigated at 1300℃. The loading-strain curves and the microstructures of the sample were compared with each other. The various of high temperature tensile behaviors was attributed to the different microstructures resulted from different high temperature pretreatments.

  14. Numerical modelling of micro-machining of f.c.c. single crystal: Influence of strain gradients

    KAUST Repository

    Demiral, Murat

    2014-11-01

    A micro-machining process becomes increasingly important with the continuous miniaturization of components used in various fields from military to civilian applications. To characterise underlying micromechanics, a 3D finite-element model of orthogonal micro-machining of f.c.c. single crystal copper was developed. The model was implemented in a commercial software ABAQUS/Explicit employing a user-defined subroutine VUMAT. Strain-gradient crystal-plasticity and conventional crystal-plasticity theories were used to demonstrate the influence of pre-existing and evolved strain gradients on the cutting process for different combinations of crystal orientations and cutting directions. Crown Copyright © 2014.

  15. Fibulin-1C, C1 Esterase Inhibitor and Glucose Regulated Protein 75 Interact with the CREC Proteins, Calumenin and Reticulocalbin

    DEFF Research Database (Denmark)

    Hansen, G. A. W.; Ludvigsen, M.; Jacobsen, C.;

    2015-01-01

    Affinity purification, immunoprecipitation, gel electrophoresis and mass spectrometry were used to identify fibulin-1C, C1 esterase inhibitor and glucose regulated protein 75, grp75, as binding partners of the CREC proteins, calumenin and reticulocalbin. Surface plasmon resonance was used to verify...... interacted with both proteins with an estimated dissociation constant at 1 mu M for reticulocalbin and 150 nM for calumenin. The interaction, at least for calumenin, was dependent upon the presence of Ca2+ with strong interaction at 3.5 mM while no detectable interaction could be found at 0.1 mM. Grp75 binds...

  16. Solvent-Free Selective Condensations Based on the Formation of the Olefinic (C=C Bond Catalyzed by Organocatalyst

    Directory of Open Access Journals (Sweden)

    Heyuan Song

    2016-07-01

    Full Text Available Pyrrolidine and its derivatives were used to catalyze aldol and Knoevenagel condensations for the formation of the olefinic (C=C bond under solvent-free conditions. The 3-pyrrolidinamine showed high activity and afforded excellent yields of α,β-unsaturated compounds. The aldol condensation of aromatic/heterocyclic aldehydes with ketones affords enones in high conversion (99.5% and selectivity (92.7%. Good to excellent yields of α,β-unsaturated compounds were obtained in the Knoevenagel condensation of aldehydes with methylene-activated substrates.

  17. Direct Construction of 4-Hydroxybenzils via Para-Selective C-C Bond Coupling of Phenols and Aryl Methyl Ketones.

    Science.gov (United States)

    Xiang, Jia-Chen; Cheng, Yan; Wang, Miao; Wu, Yan-Dong; Wu, An-Xin

    2016-09-01

    A highly para-selective C-C bond coupling is presented between phenols C(sp(2)) and aryl methyl ketones C(sp(3)), which enables the direct construction of 4-hydroxybenzil derivatives. This practical method exhibits a broad substrate scope and large-scale applicability and represents a general gateway to the hydroxybenzil natural product family. Mechanistic investigations indicated that the combination of HI with DMSO realized the oxidative carbonylation of aryl methyl ketones, while boric acid acted as a dual-functional relay reagent to promote this transformation. PMID:27513164

  18. Finding a Leucine in a Haystack: Searching the Proteome for ambigous Leucine-Aspartic Acid motifs

    KAUST Repository

    Arold, Stefan T.

    2016-01-25

    Leucine-aspartic acid (LD) motifs are short helical protein-protein interaction motifs involved in cell motility, survival and communication. LD motif interactions are also implicated in cancer metastasis and are targeted by several viruses. LD motifs are notoriously difficult to detect because sequence pattern searches lead to an excessively high number of false positives. Hence, despite 20 years of research, only six LD motif–containing proteins are known in humans, three of which are close homologues of the paxillin family. To enable the proteome-wide discovery of LD motifs, we developed LD Motif Finder (LDMF), a web tool based on machine learning that combines sequence information with structural predictions to detect LD motifs with high accuracy. LDMF predicted 13 new LD motifs in humans. Using biophysical assays, we experimentally confirmed in vitro interactions for four novel LD motif proteins. Thus, LDMF allows proteome-wide discovery of LD motifs, despite a highly ambiguous sequence pattern. Functional implications will be discussed.

  19. Automated protein motif generation in the structure-based protein function prediction tool ProMOL.

    Science.gov (United States)

    Osipovitch, Mikhail; Lambrecht, Mitchell; Baker, Cameron; Madha, Shariq; Mills, Jeffrey L; Craig, Paul A; Bernstein, Herbert J

    2015-12-01

    ProMOL, a plugin for the PyMOL molecular graphics system, is a structure-based protein function prediction tool. ProMOL includes a set of routines for building motif templates that are used for screening query structures for enzyme active sites. Previously, each motif template was generated manually and required supervision in the optimization of parameters for sensitivity and selectivity. We developed an algorithm and workflow for the automation of motif building and testing routines in ProMOL. The algorithm uses a set of empirically derived parameters for optimization and requires little user intervention. The automated motif generation algorithm was first tested in a performance comparison with a set of manually generated motifs based on identical active sites from the same 112 PDB entries. The two sets of motifs were equally effective in identifying alignments with homologs and in rejecting alignments with unrelated structures. A second set of 296 active site motifs were generated automatically, based on Catalytic Site Atlas entries with literature citations, as an expansion of the library of existing manually generated motif templates. The new motif templates exhibited comparable performance to the existing ones in terms of hit rates against native structures, homologs with the same EC and Pfam designations, and randomly selected unrelated structures with a different EC designation at the first EC digit, as well as in terms of RMSD values obtained from local structural alignments of motifs and query structures. This research is supported by NIH grant GM078077. PMID:26573864

  20. Motif Discovery in Tissue-Specific Regulatory Sequences Using Directed Information

    Directory of Open Access Journals (Sweden)

    James Douglas Engel

    2007-12-01

    Full Text Available Motif discovery for the identification of functional regulatory elements underlying gene expression is a challenging problem. Sequence inspection often leads to discovery of novel motifs (including transcription factor sites with previously uncharacterized function in gene expression. Coupled with the complexity underlying tissue-specific gene expression, there are several motifs that are putatively responsible for expression in a certain cell type. This has important implications in understanding fundamental biological processes such as development and disease progression. In this work, we present an approach to the identification of motifs (not necessarily transcription factor sites and examine its application to some questions in current bioinformatics research. These motifs are seen to discriminate tissue-specific gene promoter or regulatory regions from those that are not tissue-specific. There are two main contributions of this work. Firstly, we propose the use of directed information for such classification constrained motif discovery, and then use the selected features with a support vector machine (SVM classifier to find the tissue specificity of any sequence of interest. Such analysis yields several novel interesting motifs that merit further experimental characterization. Furthermore, this approach leads to a principled framework for the prospective examination of any chosen motif to be discriminatory motif for a group of coexpressed/coregulated genes, thereby integrating sequence and expression perspectives. We hypothesize that the discovery of these motifs would enable the large-scale investigation for the tissue-specific regulatory role of any conserved sequence element identified from genome-wide studies.

  1. Motif Discovery in Tissue-Specific Regulatory Sequences Using Directed Information

    Directory of Open Access Journals (Sweden)

    States David

    2007-01-01

    Full Text Available Motif discovery for the identification of functional regulatory elements underlying gene expression is a challenging problem. Sequence inspection often leads to discovery of novel motifs (including transcription factor sites with previously uncharacterized function in gene expression. Coupled with the complexity underlying tissue-specific gene expression, there are several motifs that are putatively responsible for expression in a certain cell type. This has important implications in understanding fundamental biological processes such as development and disease progression. In this work, we present an approach to the identification of motifs (not necessarily transcription factor sites and examine its application to some questions in current bioinformatics research. These motifs are seen to discriminate tissue-specific gene promoter or regulatory regions from those that are not tissue-specific. There are two main contributions of this work. Firstly, we propose the use of directed information for such classification constrained motif discovery, and then use the selected features with a support vector machine (SVM classifier to find the tissue specificity of any sequence of interest. Such analysis yields several novel interesting motifs that merit further experimental characterization. Furthermore, this approach leads to a principled framework for the prospective examination of any chosen motif to be discriminatory motif for a group of coexpressed/coregulated genes, thereby integrating sequence and expression perspectives. We hypothesize that the discovery of these motifs would enable the large-scale investigation for the tissue-specific regulatory role of any conserved sequence element identified from genome-wide studies.

  2. Transduction motif analysis of gastric cancer based on a human signaling network

    Energy Technology Data Exchange (ETDEWEB)

    Liu, G.; Li, D.Z.; Jiang, C.S.; Wang, W. [Fuzhou General Hospital of Nanjing Command, Department of Gastroenterology, Fuzhou, China, Department of Gastroenterology, Fuzhou General Hospital of Nanjing Command, Fuzhou (China)

    2014-04-04

    To investigate signal regulation models of gastric cancer, databases and literature were used to construct the signaling network in humans. Topological characteristics of the network were analyzed by CytoScape. After marking gastric cancer-related genes extracted from the CancerResource, GeneRIF, and COSMIC databases, the FANMOD software was used for the mining of gastric cancer-related motifs in a network with three vertices. The significant motif difference method was adopted to identify significantly different motifs in the normal and cancer states. Finally, we conducted a series of analyses of the significantly different motifs, including gene ontology, function annotation of genes, and model classification. A human signaling network was constructed, with 1643 nodes and 5089 regulating interactions. The network was configured to have the characteristics of other biological networks. There were 57,942 motifs marked with gastric cancer-related genes out of a total of 69,492 motifs, and 264 motifs were selected as significantly different motifs by calculating the significant motif difference (SMD) scores. Genes in significantly different motifs were mainly enriched in functions associated with cancer genesis, such as regulation of cell death, amino acid phosphorylation of proteins, and intracellular signaling cascades. The top five significantly different motifs were mainly cascade and positive feedback types. Almost all genes in the five motifs were cancer related, including EPOR, MAPK14, BCL2L1, KRT18, PTPN6, CASP3, TGFBR2, AR, and CASP7. The development of cancer might be curbed by inhibiting signal transductions upstream and downstream of the selected motifs.

  3. The Molecular Switching Mechanism at the Conserved D(E)RY Motif in Class-A GPCRs.

    Science.gov (United States)

    Sandoval, Angelica; Eichler, Stefanie; Madathil, Sineej; Reeves, Philip J; Fahmy, Karim; Böckmann, Rainer A

    2016-07-12

    The disruption of ionic and H-bond interactions between the cytosolic ends of transmembrane helices TM3 and TM6 of class-A (rhodopsin-like) G protein-coupled receptors (GPCRs) is a hallmark for their activation by chemical or physical stimuli. In the bovine photoreceptor rhodopsin, this is accompanied by proton uptake at Glu(134) in the class-conserved D(E)RY motif. Studies on TM3 model peptides proposed a crucial role of the lipid bilayer in linking protonation to stabilization of an active state-like conformation. However, the molecular details of this linkage could not be resolved and have been addressed in this study by molecular dynamics (MD) simulations on TM3 model peptides in a bilayer of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). We show that protonation of the conserved glutamic acid alters the peptide insertion depth in the membrane, its side-chain rotamer preferences, and stabilizes the C-terminal helical structure. These factors contribute to the rise of the side-chain pKa (> 6) and to reduced polarity around the TM3 C terminus as confirmed by fluorescence spectroscopy. Helix stabilization requires the protonated carboxyl group; unexpectedly, this stabilization could not be evoked with an amide in MD simulations. Additionally, time-resolved Fourier transform infrared (FTIR) spectroscopy of TM3 model peptides revealed a different kinetics for lipid ester carbonyl hydration, suggesting that the carboxyl is linked to more extended H-bond clusters than an amide. Remarkably, this was seen as well in DOPC-reconstituted Glu(134)- and Gln(134)-containing bovine opsin mutants and demonstrates that the D(E)RY motif is a hydrated microdomain. The function of the D(E)RY motif as a proton switch is suggested to be based on the reorganization of the H-bond network at the membrane interface. PMID:27410736

  4. A motif for reversible nitric oxide interactions in metalloenzymes.

    Science.gov (United States)

    Zhang, Shiyu; Melzer, Marie M; Sen, S Nermin; Çelebi-Ölçüm, Nihan; Warren, Timothy H

    2016-07-01

    Nitric oxide (NO) participates in numerous biological processes, such as signalling in the respiratory system and vasodilation in the cardiovascular system. Many metal-mediated processes involve direct reaction of NO to form a metal-nitrosyl (M-NO), as occurs at the Fe(2+) centres of soluble guanylate cyclase or cytochrome c oxidase. However, some copper electron-transfer proteins that bear a type 1 Cu site (His2Cu-Cys) reversibly bind NO by an unknown motif. Here, we use model complexes of type 1 Cu sites based on tris(pyrazolyl)borate copper thiolates [Cu(II)]-SR to unravel the factors involved in NO reactivity. Addition of NO provides the fully characterized S-nitrosothiol adduct [Cu(I)](κ(1)-N(O)SR), which reversibly loses NO on purging with an inert gas. Computational analysis outlines a low-barrier pathway for the capture and release of NO. These findings suggest a new motif for reversible binding of NO at bioinorganic metal centres that can interconvert NO and RSNO molecular signals at copper sites. PMID:27325092

  5. Graph animals, subgraph sampling and motif search in large networks

    CERN Document Server

    Baskerville, Kim; Paczuski, Maya

    2007-01-01

    We generalize a sampling algorithm for lattice animals (connected clusters on a regular lattice) to a Monte Carlo algorithm for `graph animals', i.e. connected subgraphs in arbitrary networks. As with the algorithm in [N. Kashtan et al., Bioinformatics 20, 1746 (2004)], it provides a weighted sample, but the computation of the weights is much faster (linear in the size of subgraphs, instead of super-exponential). This allows subgraphs with up to ten or more nodes to be sampled with very high statistics, from arbitrarily large networks. Using this together with a heuristic algorithm for rapidly classifying isomorphic graphs, we present results for two protein interaction networks obtained using the TAP high throughput method: one of Escherichia coli with 230 nodes and 695 links, and one for yeast (Saccharomyces cerevisiae) with roughly ten times more nodes and links. We find in both cases that most connected subgraphs are strong motifs (Z-scores >10) or anti-motifs (Z-scores <-10) when the null model is the...

  6. The Origin of Motif Families in Food Webs

    CERN Document Server

    Klaise, Janis

    2016-01-01

    Food webs have been found to exhibit remarkable motif profiles, patterns in the relative prevalences of all possible three-species sub-graphs, and this has been related to ecosystem properties such as stability and robustness. Analysing 46 food webs of various kinds, we find that most food webs fall into one of two distinct motif families. The separation between the families is well predicted by a global measure of hierarchical order in directed networks - trophic coherence. We find that trophic coherence is also a good predictor for the extent of omnivory, defined as the tendency of species to feed on multiple trophic levels. We compare our results to a network assembly model that admits tunable trophic coherence via a single free parameter. The model is able to generate food webs in either of the two families by varying this parameter, and correctly classifies almost all the food webs in our database. This establishes a link between global order and local preying patterns in food webs.

  7. The discodermolide hairpin structure flows from conformationally stable modular motifs.

    Science.gov (United States)

    Jogalekar, Ashutosh S; Kriel, Frederik H; Shi, Qi; Cornett, Ben; Cicero, Daniel; Snyder, James P

    2010-01-14

    (+)-Discodermolide (DDM), a polyketide macrolide from marine sponge, is a potent microtubule assembly promoter. Reported solid-state, solution, and protein-bound DDM conformations reveal the unusual result that a common hairpin conformational motif exists in all three microenvironments. No other flexible microtubule binding agent exhibits such constancy of conformation. In the present study, we combine force-field conformational searches with NMR deconvolution in different solvents to compare DDM conformers with those observed in other environments. While several conformational families are perceived, the hairpin form dominates. The stability of this motif is dictated primarily by steric factors arising from repeated modular segments in DDM composed of the C(Me)-CHX-C(Me) fragment. Furthermore, docking protocols were utilized to probe the DDM binding mode in beta-tubulin. A previously suggested pose is substantiated (Pose-1), while an alternative (Pose-2) has been identified. SAR analysis for DDM analogues differentiates the two poses and suggests that Pose-2 is better able to accommodate the biodata.

  8. A motif-independent metric for DNA sequence specificity

    Directory of Open Access Journals (Sweden)

    Pinello Luca

    2011-10-01

    Full Text Available Abstract Background Genome-wide mapping of protein-DNA interactions has been widely used to investigate biological functions of the genome. An important question is to what extent such interactions are regulated at the DNA sequence level. However, current investigation is hampered by the lack of computational methods for systematic evaluating sequence specificity. Results We present a simple, unbiased quantitative measure for DNA sequence specificity called the Motif Independent Measure (MIM. By analyzing both simulated and real experimental data, we found that the MIM measure can be used to detect sequence specificity independent of presence of transcription factor (TF binding motifs. We also found that the level of specificity associated with H3K4me1 target sequences is highly cell-type specific and highest in embryonic stem (ES cells. We predicted H3K4me1 target sequences by using the N- score model and found that the prediction accuracy is indeed high in ES cells.The software to compute the MIM is freely available at: https://github.com/lucapinello/mim. Conclusions Our method provides a unified framework for quantifying DNA sequence specificity and serves as a guide for development of sequence-based prediction models.

  9. Molecular dynamics simulation of C-C bond scission in polyethylene and linear alkanes: effects of the condensed phase.

    Science.gov (United States)

    Popov, Konstantin V; Knyazev, Vadim D

    2014-03-27

    The reaction of C-C bond scission in polyethylene chains of various lengths was studied using molecular dynamics under the conditions of vacuum and condensed phase (polymer melt). A method of assigning meaningful rate constant values to condensed-phase bond scission reactions based on a kinetic mechanism accounting for dissociation, reverse recombination, and diffusional separation of fragments was developed. The developed method accounts for such condensed-phase phenomena as cage effects and diffusion of the decay products away from the reaction site. The results of C-C scission simulations indicate that per-bond rate constants decrease by an order of magnitude as the density of the system increases from vacuum to the normal density of a polyethylene melt. Additional calculations were performed to study the dependence of the rate constant on the length of the polymer chain under the conditions of the condensed phase. The calculations demonstrate that the rate constant is independent of the degree of polymerization if polyethylene samples of different lengths are kept at the same pressure. However, if instead molecular systems of different polyethylene chain lengths decompose under the conditions of the same density, shorter chains result in higher pressures and lower rate constants. The observed effect is attributed to a higher degree of molecular crowding (lower fraction of free intermolecular space available for molecular motion) in the case of shorter molecules. PMID:24571517

  10. Preparation and characteristics of C/C composite brake disc by multi-cylindrical chemical vapor deposition processes

    Institute of Scientific and Technical Information of China (English)

    YUAN Yi-dong; ZHANG Fu-kuan; ZHOU Wan-cheng

    2005-01-01

    The C/C composite brake discs were prepared by tri-cylindrical chemical vapor deposition (CVD) process. The optimum processing parameters were as follows: deposition temperature was 830-930 ℃, the gas-flow rates of N2 and propylene were 4.8-5.2 m3/h and 5.8-6.2 m3/h, respectively, the furnace pressure was 4.5-5.5 kPa and the deposition time was 200 h.The effects of processing parameters on the densified rates, thermal-physical property and mechanical performance of C/C composite brake discs were studied. The results show that density, heat conductivity, bend strength and abrasion ratio of the multi-cylindrica brake discs are 1.02-1.78 g/cm3, 31 W/(m·K), 114 MPa and 7 μm/s, respectively, which are approximately similar to those of the single-cylindrical ones. The gas flow rate has no relation to the number of the cylinder and furnace loading. The utilization ratio of carbon can be improved by multi-cylinder CVD process without changing the characteristics of brake disc.

  11. A discrete event simulation model for evaluating the performances of an m/g/c/c state dependent queuing system.

    Directory of Open Access Journals (Sweden)

    Ruzelan Khalid

    Full Text Available M/G/C/C state dependent queuing networks consider service rates as a function of the number of residing entities (e.g., pedestrians, vehicles, and products. However, modeling such dynamic rates is not supported in modern Discrete Simulation System (DES software. We designed an approach to cater this limitation and used it to construct the M/G/C/C state-dependent queuing model in Arena software. Using the model, we have evaluated and analyzed the impacts of various arrival rates to the throughput, the blocking probability, the expected service time and the expected number of entities in a complex network topology. Results indicated that there is a range of arrival rates for each network where the simulation results fluctuate drastically across replications and this causes the simulation results and analytical results exhibit discrepancies. Detail results that show how tally the simulation results and the analytical results in both abstract and graphical forms and some scientific justifications for these have been documented and discussed.

  12. NIBLES - an HI census of stellar mass selected SDSS galaxies: I. The Nan\\c{c}ay HI survey

    CERN Document Server

    van Driel, W; Schneider, S; Lehnert, M D; Minchin, R; Blyth, S-L; Chemin, L; Hallet, N; Joseph, T; Kotze, P; Kraan-Korteweg, R C; Olofsson, A O H; Ramatsoku, M

    2016-01-01

    To investigate galaxy properties as a function of their total stellar mass, we obtained 21cm HI line observations at the 100-m class Nan\\c{c}ay Radio Telescope of 2839 galaxies from the Sloan Digital Sky Survey (SDSS) in the Local Volume (900c{c}ay Interstellar Baryons Legacy Extragalactic Survey (NIBLES) sample. They were selected evenly over their entire range of absolute SDSS z-band magnitudes (-13.5 to -24 mag), which were used as a proxy for their stellar masses. Here, a first, global presentation of the observations and basic results is given, their further analysis will be presented in other papers in this series. The galaxies were selected based on their properties, as listed in SDSS DR5. Comparing this photometry to their total HI masses, we noted that, for a few percent, the SDSS magnitudes appeared severely misunderestimated, as confirmed by our re-measurements for selected objects. Although using the later DR9 results eliminated this problem in most cases, 38...

  13. Plasma deposition of fluorocarbon thin films from c-C4F8 using pulsed and continuous rf excitation

    International Nuclear Information System (INIS)

    Fluorocarbon films of varying composition have been deposited from pulsed and continuous plasmas of octafluorocyclobutane (c-C4F8) and c-C4F8/Ar. Continuous plasma deposition rates are a very weak function of applied rf power (may be within experimental error). Pulsed plasma deposition rates are significantly lower than continuous plasma rates at the same average power. The pulsed plasma deposition rates can be attributed almost entirely to the plasma on time during the pulse, but there is a slight dependence on pulse off time. Ar addition affects the deposition rates through a residence time effect, but also affects the deposition chemistry by reducing the degree of C4F8 dissociation, resulting in more fluorinated films. Refractive indices for all films increase approximately linearly with applied rf power, with the pulsed plasma-deposited films falling on the same curve. Carbon 1s x-ray photoelectron spectroscopy shows that the continuous plasma-deposited films become increasingly fluorinated as the rf power is decreased. Pulsed plasma films are more fluorinated than similar average power continuous plasma films: 44% CF2 for 10/50 (400 W on time, 67 W average power) versus 37% for 50 W continuous. Literature and preliminary gas-phase measurements suggest that the C4F8 is not fully dissociated in either plasma system and that larger species in the gas phase may play a significant role in the deposition mechanisms

  14. First observation of the isospin violating decay $J/\\psi\\rightarrow \\Lambda\\bar{\\Sigma}^{0}+c.c.$

    CERN Document Server

    Ablikim, M; Ambrose, D J; An, F F; An, Q; An, Z H; Bai, J Z; Ban, Y; Becker, J; Berger, N; Bertani, M; Bian, J M; Boger, E; Bondarenko, O; Boyko, I; Briere, R A; Bytev, V; Cai, X; Cakir, O; Calcaterra, A; Cao, G F; Cetin, S A; Chang, J F; Chelkov, G; Chen, G; Chen, H S; Chen, J C; Chen, M L; Chen, S J; Chen, Y; Chen, Y B; Cheng, H P; Chu, Y P; Cronin-Hennessy, D; Dai, H L; Dai, J P; Dedovich, D; Deng, Z Y; Denig, A; Denysenko, I; Destefanis, M; Ding, W M; Ding, Y; Dong, L Y; Dong, M Y; Du, S X; Fang, J; Fang, S S; Fava, L; Feldbauer, F; Feng, C Q; Ferroli, R B; Fu, C D; Fu, J L; Gao, Y; Geng, C; Goetzen, K; Gong, W X; Gradl, W; Greco, M; Gu, M H; Gu, Y T; Guan, Y H; Guo, A Q; Guo, L B; Guo, Y P; Han, Y L; Hao, X Q; Harris, F A; He, K L; He, M; He, Z Y; Held, T; Heng, Y K; Hou, Z L; Hu, H M; Hu, J F; Hu, T; Huang, B; Huang, G M; Huang, J S; Huang, X T; Huang, Y P; Hussain, T; Ji, C S; Ji, Q; Ji, X B; Ji, X L; Jia, L K; Jiang, L L; Jiang, X S; Jiao, J B; Jiao, Z; Jin, D P; Jin, S; Jing, F F; Kalantar-Nayestanaki, N; Kavatsyuk, M; Kuehn, W; Lai, W; Lange, J S; Li, C H; Li, Cheng; Li, Cui; Li, D M; Li, F; Li, G; Li, H B; Li, J C; Li, K; Li, Lei; Li, N B; Li, Q J; Li, S L; Li, W D; Li, W G; Li, X L; Li, X N; Li, X Q; Li, X R; Li, Z B; Liang, H; Liang, Y F; Liang, Y T; Liao, G R; Liao, X T; Liu, B J; Liu, C L; Liu, C X; Liu, C Y; Liu, F H; Liu, Fang; Liu, Feng; Liu, H; Liu, H B; Liu, H H; Liu, H M; Liu, H W; Liu, J P; Liu, K Y; Liu, Kai; Liu, Kun; Liu, P L; Liu, S B; Liu, X; Liu, X H; Liu, Y; Liu, Y B; Liu, Z A; Liu, Zhiqiang; Liu, Zhiqing; Loehner, H; Lu, G R; Lu, H J; Lu, J G; Lu, Q W; Lu, X R; Lu, Y P; Luo, C L; Luo, M X; Luo, T; Luo, X L; Lv, M; Ma, C L; Ma, F C; Ma, H L; Ma, Q M; Ma, S; Ma, T; Ma, X Y; Ma, Y; Maas, F E; Maggiora, M; Malik, Q A; Mao, H; Mao, Y J; Mao, Z P; Messchendorp, J G; Min, J; Min, T J; Mitchell, R E; Mo, X H; Morales, C Morales; Motzko, C; Muchnoi, N Yu; Muramatsu, H; Nefedov, Y; Nicholson, C; Nikolaev, I B; Ning, Z; Olsen, S L; Ouyang, Q; Pacetti, S; Park, J W; Pelizaeus, M; Peng, H P; Peters, K; Ping, J L; Ping, R G; Poling, R; Prencipe, E; Qi, M; Qian, S; Qiao, C F; Qin, X S; Qin, Y; Qin, Z H; Qiu, J F; Rashid, K H; Rong, G; Ruan, X D; Sarantsev, A; Schaefer, B D; Schulze, J; Shao, M; Shen, C P; Shen, X Y; Sheng, H Y; Shepherd, M R; Song, X Y; Spataro, S; Spruck, B; Sun, D H; Sun, G X; Sun, J F; Sun, S S; Sun, X D; Sun, Y J; Sun, Y Z; Sun, Z J; Sun, Z T; Tang, C J; Tang, X; Tapan, X F Tang I; Thorndike, E H; Tian, H L; Toth, D; Ullrich, M; Varner, G S; Wang, B; Wang, B Q; Wang, K; Wang, L L; Wang, L S; Wang, M; Wang, P; Wang, P L; Wang, Q; Wang, Q J; Wang, S G; Wang, X L; Wang, Y D; Wang, Y F; Wang, Y Q; Wang, Z; Wang, Z G; Wang, Z Y; Wei, D H; Weidenkaff, P; Wen, Q G; Wen, S P; Werner, M; Wiedner, U; Wu, L H; Wu, N; Wu, S X; Wu, W; Wu, Z; Xia, L G; Xiao, Z J; Xie, Y G; Xiu, Q L; Xu, G F; Xu, G M; Xu, H; Xu, Q J; Xu, X P; Xu, Z R; Xue, F; Xue, Z; Yan, L; Yan, W B; Yan, Y H; Yang, H X; Yang, Y; Yang, Y X; Ye, H; Ye, M; Ye, M H; Yu, B X; Yu, C X; Yu, J S; Yu, S P; Yuan, C Z; Yuan, W L; Yuan, Y; Zafar, A A; Zallo, A; Zeng, Y; Zhang, B X; Zhang, B Y; Zhang, C C; Zhang, D H; Zhang, H H; Zhang, H Y; Zhang, J; Zhang, J Q; Zhang, J W; Zhang, J Y; Zhang, J Z; Zhang, S H; Zhang, T R; Zhang, X J; Zhang, X Y; Zhang, Y; Zhang, Y H; Zhang, Y S; Zhang, Z P; Zhang, Z Y; Zhao, G; Zhao, H S; Zhao, J W; Zhao, K X; Zhao, Lei; Zhao, Ling; Zhao, M G; Zhao, Q; Zhao, S J; Zhao, T C; Zhao, X H; Zhao, Y B; Zhao, Z G; Zhemchugov, A; Zheng, B; Zheng, J P; Zheng, Y H; Zheng, Z P; Zhong, B; Zhong, J; Zhou, L; Zhou, X K; Zhou, X R; Zhu, C; Zhu, K; Zhu, K J; Zhu, S H; Zhu, X L; Zhu, X W; Zhu, Y C; Zhu, Y M; Zhu, Y S; Zhu, Z A; Zhuang, J; Zou, B S; Zou, J H; Zuo, J X

    2012-01-01

    Using a sample of $(225.2\\pm 2.8)\\times 10^6$ $J/\\psi$ events collected with the BESIII detector, we present results of a study of $J/\\psi\\rightarrow \\gamma\\Lambda\\bar{\\Lambda}$ and report the first observation of the isospin violating decay $J/\\psi\\rightarrow\\Lambda\\bar{\\Sigma}^{0}+c.c.$, in which $\\bar{\\Sigma}^{0}$ decays to $\\gamma \\bar{\\Lambda}$. The measured branching fractions are $\\mathcal{B}(J/\\psi\\rightarrow\\bar{\\Lambda}\\Sigma^{0}$) = $(1.46\\pm0.11\\pm0.12) \\times10^{-5}$ and $\\mathcal{B}(J/\\psi\\rightarrow\\Lambda\\bar{\\Sigma^{0}}$) = $(1.37\\pm0.12\\pm0.11) \\times10^{-5}$. We search for $\\Lambda(1520) \\rightarrow \\gamma \\Lambda$ decay, and find no evident signal, and an upper limit for the product branching fraction $\\mathcal{B}(J/\\psi\\rightarrow\\Lambda\\bar{\\Lambda}(1520)+c.c.)\\times \\mathcal{B}(\\Lambda(1520)\\rightarrow\\gamma\\Lambda)<4.1 \\times10^{-6}$ is set at the 90% confidence level. We also report the observation of $\\eta_{c}\\rightarrow\\Lambda\\bar{\\Lambda}$ in $J/\\psi \\rightarrow \\gamma \\eta_{c}$...

  15. Effects of chemokine (C–C motif) ligand 1 on microglial function

    International Nuclear Information System (INIS)

    Highlights: •CCR8, a specific receptor for CCL-1, was expressed on primary cultured microglia. •Expression of CCR-8 in microglia was upregulated in the presence of CCL-1. •CCL-1 increased motility, proliferation and phagocytosis of cultured microglia. •CCL-1promoted BDNF and IL-6 mRNA, and the release of NO from microglia. •CCL-1 activates microglia and may contribute to the development of neuropathic pain. -- Abstract: Microglia, which constitute the resident macrophages of the central nervous system (CNS), are generally considered as the primary immune cells in the brain and spinal cord. Microglial cells respond to various factors which are produced following nerve injury of multiple aetiologies and contribute to the development of neuronal disease. Chemokine (C–C motif) ligand 1 (CCL-1), a well-characterized chemokine secreted by activated T cells, has been shown to play an important role in neuropathic pain induced by nerve injury and is also produced in various cell types in the CNS, especially in dorsal root ganglia (DRG). However, the role of CCL-1 in the CNS and the effects on microglia remains unclear. Here we showed the multiple effects of CCL-1 on microglia. We first showed that CCR-8, a specific receptor for CCL-1, was expressed on primary cultured microglia, as well as on astrocytes and neurons, and was upregulated in the presence of CCL-1. CCL-1 at concentration of 1 ng/ml induced chemotaxis, increased motility at a higher concentration (100 ng/ml), and increased proliferation and phagocytosis of cultured microglia. CCL-1 also activated microglia morphologically, promoted mRNA levels for brain-derived neurotrophic factor (BDNF) and IL-6, and increased the release of nitrite from microglia. These indicate that CCL-1 has a role as a mediator in neuron-glia interaction, which may contribute to the development of neurological diseases, especially in neuropathic pain

  16. Effects of chemokine (C–C motif) ligand 1 on microglial function

    Energy Technology Data Exchange (ETDEWEB)

    Akimoto, Nozomi [Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Ifuku, Masataka [Laboratory of Integrative Physiology, Graduate School of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Mori, Yuki [Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Noda, Mami, E-mail: noda@phar.kyushu-u.ac.jp [Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)

    2013-07-05

    Highlights: •CCR8, a specific receptor for CCL-1, was expressed on primary cultured microglia. •Expression of CCR-8 in microglia was upregulated in the presence of CCL-1. •CCL-1 increased motility, proliferation and phagocytosis of cultured microglia. •CCL-1promoted BDNF and IL-6 mRNA, and the release of NO from microglia. •CCL-1 activates microglia and may contribute to the development of neuropathic pain. -- Abstract: Microglia, which constitute the resident macrophages of the central nervous system (CNS), are generally considered as the primary immune cells in the brain and spinal cord. Microglial cells respond to various factors which are produced following nerve injury of multiple aetiologies and contribute to the development of neuronal disease. Chemokine (C–C motif) ligand 1 (CCL-1), a well-characterized chemokine secreted by activated T cells, has been shown to play an important role in neuropathic pain induced by nerve injury and is also produced in various cell types in the CNS, especially in dorsal root ganglia (DRG). However, the role of CCL-1 in the CNS and the effects on microglia remains unclear. Here we showed the multiple effects of CCL-1 on microglia. We first showed that CCR-8, a specific receptor for CCL-1, was expressed on primary cultured microglia, as well as on astrocytes and neurons, and was upregulated in the presence of CCL-1. CCL-1 at concentration of 1 ng/ml induced chemotaxis, increased motility at a higher concentration (100 ng/ml), and increased proliferation and phagocytosis of cultured microglia. CCL-1 also activated microglia morphologically, promoted mRNA levels for brain-derived neurotrophic factor (BDNF) and IL-6, and increased the release of nitrite from microglia. These indicate that CCL-1 has a role as a mediator in neuron-glia interaction, which may contribute to the development of neurological diseases, especially in neuropathic pain.

  17. Infiltration of Neutrophils and Eosinophils during Allergic Inflammation is Regulated by the Inhibitory Receptor gp-49B

    Science.gov (United States)

    gp49B, an Ig-like receptor, negatively regulates the activity of mast cells and neutrophils through cytoplasmic immuno-receptor tyrosine-based inhibition motifs (ITIM). To further characterize the role of gp49B in vivo, gp49B-deficient mice were tested in two allergic models. Responses to ragweed (R...

  18. Over-represented localized sequence motifs in ribosomal protein gene promoters of basal metazoans.

    Science.gov (United States)

    Perina, Drago; Korolija, Marina; Roller, Maša; Harcet, Matija; Jeličić, Branka; Mikoč, Andreja; Cetković, Helena

    2011-07-01

    Equimolecular presence of ribosomal proteins (RPs) in the cell is needed for ribosome assembly and is achieved by synchronized expression of ribosomal protein genes (RPGs) with promoters of similar strengths. Over-represented motifs of RPG promoter regions are identified as targets for specific transcription factors. Unlike RPs, those motifs are not conserved between mammals, drosophila, and yeast. We analyzed RPGs proximal promoter regions of three basal metazoans with sequenced genomes: sponge, cnidarian, and placozoan and found common features, such as 5'-terminal oligopyrimidine tracts and TATA-boxes. Furthermore, we identified over-represented motifs, some of which displayed the highest similarity to motifs abundant in human RPG promoters and not present in Drosophila or yeast. Our results indicate that humans over-represented motifs, as well as corresponding domains of transcription factors, were established very early in metazoan evolution. The fast evolving nature of RPGs regulatory network leads to formation of other, lineage specific, over-represented motifs. PMID:21457775

  19. Sequence Length Limits for Controlling False Positives in Discovering Nucleotide Sequence Motifs

    Institute of Scientific and Technical Information of China (English)

    CHEN Lei; QiAN Zi-liang

    2008-01-01

    In the study of motif discovery, especially the transcription factor DNA binding sites discovery, a too long input sequence would return non-informative motifs rather than those biological functional motifs. This paper gave theoretical analyses and computational experiments to suggest the length limits of the input sequence. When the sequence length exceeds a certain critical point, the probability of discovering the motif decreases sharply. The work not only gave an explanation on the unsatisfying results of the existed motif discovery problems that the input sequence length might be too long and exceed the point, but also provided an estimation of input sequence length we should accept to get more meaningful and reliable results in motif discovery.

  20. N-terminal tetrapeptide T/SPLH motifs contribute to multimodal activation of human TRPA1 channel

    Science.gov (United States)

    Hynkova, Anna; Marsakova, Lenka; Vaskova, Jana; Vlachova, Viktorie

    2016-06-01

    Human transient receptor potential ankyrin channel 1 (TRPA1) is a polymodal sensor implicated in pain, inflammation and itching. An important locus for TRPA1 regulation is the cytoplasmic N-terminal domain, through which various exogenous electrophilic compounds such as allyl-isothiocyanate from mustard oil or cinnamaldehyde from cinnamon activate primary afferent nociceptors. This major region is comprised of a tandem set of 17 ankyrin repeats (AR1-AR17), five of them contain a strictly conserved T/SPLH tetrapeptide motif, a hallmark of an important and evolutionarily conserved contribution to conformational stability. Here, we characterize the functional consequences of putatively stabilizing and destabilizing mutations in these important structural units and identify AR2, AR6, and AR11-13 to be distinctly involved in the allosteric activation of TRPA1 by chemical irritants, cytoplasmic calcium, and membrane voltage. Considering the potential involvement of the T/SP motifs as putative phosphorylation sites, we also show that proline-directed Ser/Thr kinase CDK5 modulates the activity of TRPA1, and that T673 outside the AR-domain is its only possible target. Our data suggest that the most strictly conserved N-terminal ARs define the energetics of the TRPA1 channel gate and contribute to chemical-, calcium- and voltage-dependence.

  1. N-terminal tetrapeptide T/SPLH motifs contribute to multimodal activation of human TRPA1 channel.

    Science.gov (United States)

    Hynkova, Anna; Marsakova, Lenka; Vaskova, Jana; Vlachova, Viktorie

    2016-01-01

    Human transient receptor potential ankyrin channel 1 (TRPA1) is a polymodal sensor implicated in pain, inflammation and itching. An important locus for TRPA1 regulation is the cytoplasmic N-terminal domain, through which various exogenous electrophilic compounds such as allyl-isothiocyanate from mustard oil or cinnamaldehyde from cinnamon activate primary afferent nociceptors. This major region is comprised of a tandem set of 17 ankyrin repeats (AR1-AR17), five of them contain a strictly conserved T/SPLH tetrapeptide motif, a hallmark of an important and evolutionarily conserved contribution to conformational stability. Here, we characterize the functional consequences of putatively stabilizing and destabilizing mutations in these important structural units and identify AR2, AR6, and AR11-13 to be distinctly involved in the allosteric activation of TRPA1 by chemical irritants, cytoplasmic calcium, and membrane voltage. Considering the potential involvement of the T/SP motifs as putative phosphorylation sites, we also show that proline-directed Ser/Thr kinase CDK5 modulates the activity of TRPA1, and that T673 outside the AR-domain is its only possible target. Our data suggest that the most strictly conserved N-terminal ARs define the energetics of the TRPA1 channel gate and contribute to chemical-, calcium- and voltage-dependence. PMID:27345869

  2. Vampirism today : the change of the vampire motif from the gothic novel to today's fantasy literature

    OpenAIRE

    2009-01-01

    This thesis examins the change of the vampire motif throughout time. How have vampires and their clichés changed and why? Starting with a brief examination of the 'classical' litarary vampire, I mainly focus on contemporary fantasy literature by discussing recent works of vampire fiction. The adaptation of the vampire motif in role-playing games will as well be discussed as the effects the vampire film had on the motif.

  3. Belief-propagation algorithm and the Ising model on networks with arbitrary distributions of motifs

    OpenAIRE

    Yoon, S; Goltsev, A. V.; Dorogovtsev, S. N.; Mendes, J. F. F.

    2011-01-01

    We generalize the belief-propagation algorithm to sparse random networks with arbitrary distributions of motifs (triangles, loops, etc.). Each vertex in these networks belongs to a given set of motifs (generalization of the configuration model). These networks can be treated as sparse uncorrelated hypergraphs in which hyperedges represent motifs. Here a hypergraph is a generalization of a graph, where a hyperedge can connect any number of vertices. These uncorrelated hypergraphs are tree-like...

  4. An analysis of the positional distribution of DNA motifs in promoter regions and its biological relevance

    OpenAIRE

    Vinga Susana; Casimiro Ana C; Freitas Ana T; Oliveira Arlindo L

    2008-01-01

    Abstract Background Motif finding algorithms have developed in their ability to use computationally efficient methods to detect patterns in biological sequences. However the posterior classification of the output still suffers from some limitations, which makes it difficult to assess the biological significance of the motifs found. Previous work has highlighted the existence of positional bias of motifs in the DNA sequences, which might indicate not only that the pattern is important, but als...

  5. NestedMICA as an ab initio protein motif discovery tool

    Directory of Open Access Journals (Sweden)

    Down Thomas A

    2008-01-01

    Full Text Available Abstract Background Discovering overrepresented patterns in amino acid sequences is an important step in protein functional element identification. We adapted and extended NestedMICA, an ab initio motif finder originally developed for finding transcription binding site motifs, to find short protein signals, and compared its performance with another popular protein motif finder, MEME. NestedMICA, an open source protein motif discovery tool written in Java, is driven by a Monte Carlo technique called Nested Sampling. It uses multi-class sequence background models to represent different "uninteresting" parts of sequences that do not contain motifs of interest. In order to assess NestedMICA as a protein motif finder, we have tested it on synthetic datasets produced by spiking instances of known motifs into a randomly selected set of protein sequences. NestedMICA was also tested using a biologically-authentic test set, where we evaluated its performance with respect to varying sequence length. Results Generally NestedMICA recovered most of the short (3–9 amino acid long test protein motifs spiked into a test set of sequences at different frequencies. We showed that it can be used to find multiple motifs at the same time, too. In all the assessment experiments we carried out, its overall motif discovery performance was better than that of MEME. Conclusion NestedMICA proved itself to be a robust and sensitive ab initio protein motif finder, even for relatively short motifs that exist in only a small fraction of sequences. Availability NestedMICA is available under the Lesser GPL open-source license from: http://www.sanger.ac.uk/Software/analysis/nmica/

  6. Recruitment of SHP-1 protein tyrosine phosphatase and signalling by a chimeric T-cell receptor-killer inhibitory receptor

    DEFF Research Database (Denmark)

    Christensen, M D; Geisler, C

    2000-01-01

    Receptors expressing the immunoreceptor tyrosine-based inhibitory motif (ITIM) in their cytoplasmic tail play an important role in the negative regulation of natural killer and B-cell activation. A subpopulation of T cells expresses the ITIM containing killer cell inhibitory receptor (KIR), which...... recognize MHC class I molecules. Following coligation of KIR with an activating receptor, the tyrosine in the ITIM is phosphorylated and the cytoplasmic protein tyrosine phosphatase SHP-1 is recruited to the ITIM via its SH2 domains. It is still not clear how SHP-1 affects T-cell receptor (TCR) signalling....... In this study, we constructed a chimeric TCR-KIR receptor. We demonstrated that SHP-1 is recruited to the chimeric TCR-KIR receptor following T-cell stimulation with either anti-TCR monoclonal antibody (MoAb) or superantigen. However, in spite of this we could not detect any effect of SHP-1 on TCR signalling...

  7. A motif extraction algorithm based on hashing and modulo-4 arithmetic.

    Science.gov (United States)

    Sheng, Huitao; Mehrotra, Kishan; Mohan, Chilukuri; Raina, Ramesh

    2008-01-01

    We develop an algorithm to identify cis-elements in promoter regions of coregulated genes. This algorithm searches for subsequences of desired length whose frequency of occurrence is relatively high, while accounting for slightly perturbed variants using hash table and modulo arithmetic. Motifs are evaluated using profile matrices and higher-order Markov background model. Simulation results show that our algorithm discovers more motifs present in the test sequences, when compared with two well-known motif-discovery tools (MDScan and AlignACE). The algorithm produces very promising results on real data set; the output of the algorithm contained many known motifs.

  8. Mapping network motif tunability and robustness in the design of synthetic signaling circuits.

    Directory of Open Access Journals (Sweden)

    Sergio Iadevaia

    Full Text Available Cellular networks are highly dynamic in their function, yet evolutionarily conserved in their core network motifs or topologies. Understanding functional tunability and robustness of network motifs to small perturbations in function and structure is vital to our ability to synthesize controllable circuits. In establishing core sets of network motifs, we selected topologies that are overrepresented in mammalian networks, including the linear, feedback, feed-forward, and bifan circuits. Static and dynamic tunability of network motifs were defined as the motif ability to respectively attain steady-state or transient outputs in response to pre-defined input stimuli. Detailed computational analysis suggested that static tunability is insensitive to the circuit topology, since all of the motifs displayed similar ability to attain predefined steady-state outputs in response to constant inputs. Dynamic tunability, in contrast, was tightly dependent on circuit topology, with some motifs performing superiorly in achieving observed time-course outputs. Finally, we mapped dynamic tunability onto motif topologies to determine robustness of motif structures to changes in topology and identify design principles for the rational assembly of robust synthetic networks.

  9. Comparative genomic analysis of upstream miRNA regulatory motifs in Caenorhabditis.

    Science.gov (United States)

    Jovelin, Richard; Krizus, Aldis; Taghizada, Bakhtiyar; Gray, Jeremy C; Phillips, Patrick C; Claycomb, Julie M; Cutter, Asher D

    2016-07-01

    MicroRNAs (miRNAs) comprise a class of short noncoding RNA molecules that play diverse developmental and physiological roles by controlling mRNA abundance and protein output of the vast majority of transcripts. Despite the importance of miRNAs in regulating gene function, we still lack a complete understanding of how miRNAs themselves are transcriptionally regulated. To fill this gap, we predicted regulatory sequences by searching for abundant short motifs located upstream of miRNAs in eight species of Caenorhabditis nematodes. We identified three conserved motifs across the Caenorhabditis phylogeny that show clear signatures of purifying selection from comparative genomics, patterns of nucleotide changes in motifs of orthologous miRNAs, and correlation between motif incidence and miRNA expression. We then validated our predictions with transgenic green fluorescent protein reporters and site-directed mutagenesis for a subset of motifs located in an enhancer region upstream of let-7 We demonstrate that a CT-dinucleotide motif is sufficient for proper expression of GFP in the seam cells of adult C. elegans, and that two other motifs play incremental roles in combination with the CT-rich motif. Thus, functional tests of sequence motifs identified through analysis of molecular evolutionary signatures provide a powerful path for efficiently characterizing the transcriptional regulation of miRNA genes. PMID:27140965

  10. Antigen receptor signaling: integration of protein tyrosine kinase functions.

    Science.gov (United States)

    Tamir, I; Cambier, J C

    1998-09-17

    Antigen receptors on T and B cells function to transduce signals leading to a variety of biologic responses minimally including antigen receptor editing, apoptotic death, developmental progression, cell activation, proliferation and survival. The response to antigen depends upon antigen affinity and valence, involvement of coreceptors in signaling and differentiative stage of the responding cell. The requirement that these receptors integrate signals that drive an array of responses may explain their evolved structural complexity. Antigen receptors are composed of multiple subunits compartmentalized to provide antigen recognition and signal transduction function. In lieu of on-board enzymatic activity these receptors rely on associated Protein Tyrosine Kinases (PTKs) for their signaling function. By aggregating the receptors, and hence their appended PTKs, antigens induce PTK transphosphorylation, activating them to phosphorylate the receptor within conserved motifs termed Immunoreceptor Tyrosine-based Activation Motifs (ITAMs) found in transducer subunits. The tyrosyl phosphorylated ITAMs then interact with Src Homology 2 (SH2) domains within the PTKs leading to their further activation. As receptor phosphorylation is amplified, other effectors, such as Shc, dock by virtue of SH2 binding, and serve, in-turn, as substrates for these PTKs. This sequence of events not only provides a signal amplification mechanism by combining multiple consecutive steps with positive feedback, but also allows for signal diversification by differential recruitment of effectors that provide access to distinct parallel downstream signaling pathways. The subject of antigen receptor signaling has been recently reviewed in depth (DeFranco, 1997; Kurosaki, 1997). Here we discuss the biochemical basis of antigen receptor signal transduction, using the B cell receptor (BCR) as a paradigm, with specific emphasis on the involved PTKs. We review several specific mechanisms by which responses

  11. Motif-Driven Design of Protein-Protein Interfaces.

    Science.gov (United States)

    Silva, Daniel-Adriano; Correia, Bruno E; Procko, Erik

    2016-01-01

    Protein-protein interfaces regulate many critical processes for cellular function. The ability to accurately control and regulate these molecular interactions is of major interest for biomedical and synthetic biology applications, as well as to address fundamental biological questions. In recent years, computational protein design has emerged as a tool for designing novel protein-protein interactions with functional relevance. Although attractive, these computational tools carry a steep learning curve. In order to make some of these methods more accessible, we present detailed descriptions and examples of ROSETTA computational protocols for the design of functional protein binders using seeded protein interface design. In these protocols, a motif of known structure that interacts with the target site is grafted into a scaffold protein, followed by design of the surrounding interaction surface. PMID:27094298

  12. Appearance of the bulk motif in Al clusters

    Science.gov (United States)

    Sun, Jiao; Lu, Wen-Cai; Li, Ze-Sheng; Wang, C. Z.; Ho, K. M.

    2008-07-01

    We have performed an unbiased search for the lowest-energy structures of medium-sized aluminum clusters Aln (n=19-26) using a genetic algorithm (GA) coupled with a tight-binding interatomic potential. Structural candidates obtained from our GA search were further optimized using density functional theory. It is found that the double icosahedron is not the most stable structure for Al19 but serves as the core for Al20 and Al21. The lowest-energy structures of Aln are found to undergo a transition to an aluminum bulk motif above Al23. In particular, the lowest-energy structure of Al26 is almost a fragment of the bulk face-centered-cubic crystal except for the stacking fault at the bottom layer. Anion clusters were also studied.

  13. A cooperative fast annealing coevolutionary algorithm for protein motif extraction

    Institute of Scientific and Technical Information of China (English)

    CHEN Chao; TIAN YuanXin; ZOU XiaoYong; CAI PeiXiang; MO JinYuan

    2007-01-01

    By integrating the cooperative approach with the fast annealing coevolutionary algorithm (FAEA), a so-called cooperative fast annealing coevolutionary algorithm (CFACA) is presented in this paper for the purpose of solving high-dimensional problems. After the partition of the search space in CFACA, each smaller one is then searched by a separate FAEA. The fitness function is evaluated by combining sub-solutions found by each of the FAEAs. It demonstrates that the CFACA outperforms the FAEA in the domain of function optimization, especially in terms of convergence rate. The current algorithm is also applied to a real optimization problem of protein motif extraction. And a satisfactory result has been obtained with the accuracy of prediction achieving 67.0%, which is in agreement with the result in the PROSITE database.

  14. Sequential dynamics in the motif of excitatory coupled elements

    Science.gov (United States)

    Korotkov, Alexander G.; Kazakov, Alexey O.; Osipov, Grigory V.

    2015-11-01

    In this article a new model of motif (small ensemble) of neuron-like elements is proposed. It is built with the use of the generalized Lotka-Volterra model with excitatory couplings. The main motivation for this work comes from the problems of neuroscience where excitatory couplings are proved to be the predominant type of interaction between neurons of the brain. In this paper it is shown that there are two modes depending on the type of coupling between the elements: the mode with a stable heteroclinic cycle and the mode with a stable limit cycle. Our second goal is to examine the chaotic dynamics of the generalized three-dimensional Lotka-Volterra model.

  15. The sword motif 'n Matthew 10:34

    Directory of Open Access Journals (Sweden)

    David C. Sim

    2000-01-01

    Full Text Available 'n Mathew 10:34 Jesus uters a very dificult saying. He claims that he has not come to bring peace, but a sword. The form of this saying does not trace back to the historical Jesus; it is the product of Matthew's redaction of a Q passage which is found 'n a more original form 'n Luke 12:51. What did the evangelist mean when he wrote that Jesus brought a sword? 'n the Hebrew scriptures the sword was acommon symbol for the judgement and punishment of God, and 'n later times it represented a number of themes associated with the eschaton. It is argued 'n this study that Mathew, who was fully immersed 'n the apocalyptic-eschatological traditions of his day, probably used the sword motif 'n Matthew 10:34 to symbolise anumber of important eschatological events.

  16. Study on online community user motif using web usage mining

    Science.gov (United States)

    Alphy, Meera; Sharma, Ajay

    2016-04-01

    The Web usage mining is the application of data mining, which is used to extract useful information from the online community. The World Wide Web contains at least 4.73 billion pages according to Indexed Web and it contains at least 228.52 million pages according Dutch Indexed web on 6th august 2015, Thursday. It’s difficult to get needed data from these billions of web pages in World Wide Web. Here is the importance of web usage mining. Personalizing the search engine helps the web user to identify the most used data in an easy way. It reduces the time consumption; automatic site search and automatic restore the useful sites. This study represents the old techniques to latest techniques used in pattern discovery and analysis in web usage mining from 1996 to 2015. Analyzing user motif helps in the improvement of business, e-commerce, personalisation and improvement of websites.

  17. Developing conjugated polymers with high electron affinity by replacing a C-C unit with a B←N unit.

    Science.gov (United States)

    Dou, Chuandong; Ding, Zicheng; Zhang, Zijian; Xie, Zhiyuan; Liu, Jun; Wang, Lixiang

    2015-03-16

    The key parameters of conjugated polymers are lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) energy levels. Few approaches can simultaneously lower LUMO and HOMO energy levels of conjugated polymers to a large extent (>0.5 eV). Disclosed herein is a novel strategy to decrease both LUMO and HOMO energy levels of conjugated polymers by about 0.6 eV through replacement of a C-C unit by a B←N unit. The replacement makes the resulting polymer transform from an electron donor into an electron acceptor, and is proven by fluorescence quenching experiments and the photovoltaic response. This work not only provides an effective approach to tune the LUMO/HOMO energy levels of conjugated polymers, but also uses organic boron chemistry as a new toolbox to develop conjugated polymers with high electron affinity for polymer optoelectronic devices.

  18. SiC/Si-W-Mo coating for protection of C/C composites at 1873 K

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    In order to prevent carbon/carbon composites from oxidation at 1873 K,an efficient oxidation protective SiC/Si-W-Mo coating was prepared by a two-step pack cementation technique.The microstmctures and the phase composition of the as-received multi-coating were examined by scanning electron microscopy (SEND and X-ray diffraction (XRD).It is seen that the compact multi-coating is composed of α-SiC,Si,and (WxMo1-x)Si2·Oxidation test shows that,after oxidation at 1873 K in air for 102 h and thermal cycling between 1873 K and room temperature for 10 times,the weight loss of the SiC/Si-W-Mo coated C/C composites is only 0.26%.The invalidation of the multi-coating is attributed to the formation of penetrable cracks in the coating.

  19. Structure and function of the human megalin receptor

    DEFF Research Database (Denmark)

    Dagil, Robert

    . The extracellular domain of megalin consists of several modular domains, of which the most abundant are the ligand binding complement type (CR) domains, that are divided into four clusters separated by YWTD -propeller domains. The broad ligand binding profile has associated megalin with the unwanted cellular uptake....... Recently, structural data has provided direct proof that the -propeller domains from the lipoprotein receptor family actively engage in ligand binding. Previously, these domains were thought to serve as ’spacer regions’ in the extracellular domain. By analyzing the structural data a number of simple ligand...... binding motifs were identified and an analysis of the distribution of these simple motifs in -propeller domains throughout the LRP family was performed in order to identify -propellers capable of ligand binding. The analysis showed that several -propeller domains have ligand binding motifs, indicating...

  20. Structural fragment clustering reveals novel structural and functional motifs in α-helical transmembrane proteins

    Directory of Open Access Journals (Sweden)

    Vassilev Boris

    2010-04-01

    Full Text Available Abstract Background A large proportion of an organism's genome encodes for membrane proteins. Membrane proteins are important for many cellular processes, and several diseases can be linked to mutations in them. With the tremendous growth of sequence data, there is an increasing need to reliably identify membrane proteins from sequence, to functionally annotate them, and to correctly predict their topology. Results We introduce a technique called structural fragment clustering, which learns sequential motifs from 3D structural fragments. From over 500,000 fragments, we obtain 213 statistically significant, non-redundant, and novel motifs that are highly specific to α-helical transmembrane proteins. From these 213 motifs, 58 of them were assigned to function and checked in the scientific literature for a biological assessment. Seventy percent of the motifs are found in co-factor, ligand, and ion binding sites, 30% at protein interaction interfaces, and 12% bind specific lipids such as glycerol or cardiolipins. The vast majority of motifs (94% appear across evolutionarily unrelated families, highlighting the modularity of functional design in membrane proteins. We describe three novel motifs in detail: (1 a dimer interface motif found in voltage-gated chloride channels, (2 a proton transfer motif found in heme-copper oxidases, and (3 a convergently evolved interface helix motif found in an aspartate symporter, a serine protease, and cytochrome b. Conclusions Our findings suggest that functional modules exist in membrane proteins, and that they occur in completely different evolutionary contexts and cover different binding sites. Structural fragment clustering allows us to link sequence motifs to function through clusters of structural fragments. The sequence motifs can be applied to identify and characterize membrane proteins in novel genomes.

  1. Functional significance of vitamin D receptor FokI polymorphism in human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Fatouma Alimirah

    Full Text Available BACKGROUND: The FokI vitamin D receptor (VDR polymorphism results in different translation initiation sites on VDR. In the VDRff variant, initiation of translation occurs at the first ATG site, giving rise to a full length VDR protein of 427 amino acids. Conversely, in the VDRFF variant, translation begins at the second ATG site, resulting in a truncated protein with three less amino acids. Epidemiological studies have paradoxically implicated this polymorphism with increased breast cancer risk. 1α,25 (OH(2D(3, the active metabolite of vitamin D, is known to inhibit cell proliferation, induce apoptosis and potentiate differentiation in human breast cancer cells. It is well documented that 1α,25 (OH(2D(3 downregulates estrogen receptor α expression and inhibits estrogen mediated signaling in these cells. The functional significance of the VDR FokI polymorphism in vitamin D action is undefined. METHODS/FINDINGS: To elucidate the functional role of FokI polymorphism in breast cancer, MCF-7-Vector, MCF-7-VDRff and MCF-7-VDRFF stable cell lines were established from parental MCF-7 cells as single-cell clones. In response to 1α,25 (OH(2D(3 treatments, cell growth was inhibited by 60% in VDRFF cells compared to 28% in VDRff cells. The induction of the vitamin D target gene CYP24A1 mRNA was 1.8 fold higher in VDRFF cells than in VDRff cells. Estrogen receptor-α protein expression was downregulated by 62% in VDRFF cells compared to 25% in VDRff cells. VDR protein stability was greater in MCF-7-VDRFF cells in the presence of cycloheximide. PCR array analyses of VDRff and VDRFF cells revealed increased basal expression levels of pro-inflammatory genes Cyclooxygenase-2, Interleukin-8 and Chemokine (C-C Motif Ligand 2 in MCF-7-VDRff cells by 14, 52.7 and 5 fold, respectively. CONCLUSIONS/SIGNIFICANCE: These results suggest that a VDRff genotype may play a role in amplifying aggressive breast cancer, paving the way for understanding why some breast

  2. First principles study of the electronic and magnetic structures and bonding properties of UCoC2 ternary, characteristic of C-C units

    Science.gov (United States)

    Matar, Samir F.

    2013-03-01

    The electronic structure of UCoC2, a di-carbide with the C-C units is examined from ab initio with an assessment of the properties of chemical bonding. The energy-volume equation of state shows large anisotropy effects due to C-C alignment along tetragonal c-axis leading to high linear incompressibility. Relevant features of selective bonding of uranium and cobalt with carbon at two different Wyckoff sites and strong C-C interactions are remarkable. The vibrational frequencies for C⋯C stretching modes indicate closer behavior to aliphatic C-C rather than Cdbnd C double bond. A ferromagnetic ground state is proposed from the calculations.

  3. Synthesis of SiC decorated carbonaceous nanorods and its hierarchical composites Si@SiC@C for high-performance lithium ion batteries

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chundong [School of Optical and Electronic Information, Huazhong University of Science and Technology, Wuhan 430074 (China); Center of Super-Diamond and Advanced Films (COSDAF), Department of Physics and Materials Science, City University of Hong Kong, Hong Kong SAR (China); Li, Yi, E-mail: liyi@suda.edu.cn [College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou (China); Center of Super-Diamond and Advanced Films (COSDAF), Department of Physics and Materials Science, City University of Hong Kong, Hong Kong SAR (China); Ostrikov, Kostya [School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, Queensland 4000 (Australia); Plasma Nanoscience, Industrial Innovation Program, CSIRO Manufacturing Flagship, Lindfield, New South Wales 2070 (Australia); Yang, Yonggang [College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou (China); Zhang, Wenjun, E-mail: apwjzh@cityu.edu.hk [Center of Super-Diamond and Advanced Films (COSDAF), Department of Physics and Materials Science, City University of Hong Kong, Hong Kong SAR (China)

    2015-10-15

    SiC- based nanomaterials possess superior electric, thermal and mechanical properties. However, due to the tricky synthesis process, which needs to be carried out under high temperature with multi-step reaction procedures, the further application is dramatically limited. Herein, a simple as well as a controllable approach is proposed for synthesis of SiC- based nanostructures under low temperature. Phenyl-bridged polysilsesquioxane was chosen as the starting material to react with magnesium at 650 °C, following which SiC@C nanocomposites were finally obtained, and it maintains the original bent rod-like architecture of polysilsesquioxanes. The possible formation process for the nanocomposites can proposed as well. The electrochemical behaviour of nanocomposites was accessed, verifying that the synthesized SiC@C nanocomposites deliver good electrochemical performance. Moreover, SiC@C also shows to be a promising scaffold in supporting Si thin film electrode in achieving stable cycling performance in lithium ion batteries. - Highlights: • SiC@C bent nanorods were synthesized with a magnesium reaction approach. • Carbon nanorod spines studded with ultrafine β-SiC nanocrystallines was realized. • The synthesized SiC@C keeps the original rod-like structure of polysilsesquioxanes. • The possible formation process for the nanocomposites was analysed and proposed. • Si@SiC@C nanocomposites reveal good electrochemical performance in LIBs.

  4. Abundance Anomaly of the $^{13}$C Isotopic Species of c-C$_3$H$_2$ in the Low-Mass Star Formation Region L1527

    CERN Document Server

    Yoshida, Kento; Tokudome, Tomoya; Lopez-Sepulcre, Ana; Watanabe, Yoshimasa; Takano, Shuro; Lefloch, Bertrand; Ceccarelli, Cecilia; Bachiller, Rafael; Caux, Emmanuel; Vastel, Charlotte; Yamamoto, Satoshi

    2015-01-01

    The rotational spectral lines of c-C$_3$H$_2$ and two kinds of the $^{13}$C isotopic species, c-$^{13}$CCCH$_2$ ($C_{2v}$ symmetry) and c-CC$^{13}$CH$_2$ ($C_s$ symmetry) have been observed in the 1-3 mm band toward the low-mass star-forming region L1527. We have detected 7, 3, and 6 lines of c-C$_3$H$_2$, c-$^{13}$CCCH$_2$ , and c-CC$^{13}$CH$_2$, respectively, with the Nobeyama 45 m telescope, and 34, 6, and 13 lines, respectively, with the IRAM 30 m telescope, where 7, 2, and 2 transitions, respectively, are observed with the both telescopes. With these data, we have evaluated the column densities of the normal and $^{13}$C isotopic species. The [c-C$_3$H$_2$]/[c-$^{13}$CCCH$_2$] ratio is determined to be $310\\pm80$, while the [c-C$_3$H$_2$]/[c-CC$^{13}$CH$_2$] ratio is determined to be $61\\pm11$. The [c-C$_3$H$_2$]/[c-$^{13}$CCCH$_2$] and [c-C$_3$H$_2$]/[c-CC$^{13}$CH$_2$] ratios expected from the elemental $^{12}$C/$^{13}$C ratio are 60-70 and 30-35, respectively, where the latter takes into account the ...

  5. The EDLL motif: a potent plant transcriptional activation domain from AP2/ERF transcription factors.

    Science.gov (United States)

    Tiwari, Shiv B; Belachew, Alemu; Ma, Siu Fong; Young, Melinda; Ade, Jules; Shen, Yu; Marion, Colleen M; Holtan, Hans E; Bailey, Adina; Stone, Jeffrey K; Edwards, Leslie; Wallace, Andreah D; Canales, Roger D; Adam, Luc; Ratcliffe, Oliver J; Repetti, Peter P

    2012-06-01

    In plants, the ERF/EREBP family of transcriptional regulators plays a key role in adaptation to various biotic and abiotic stresses. These proteins contain a conserved AP2 DNA-binding domain and several uncharacterized motifs. Here, we describe a short motif, termed 'EDLL', that is present in AtERF98/TDR1 and other clade members from the same AP2 sub-family. We show that the EDLL motif, which has a unique arrangement of acidic amino acids and hydrophobic leucines, functions as a strong activation domain. The motif is transferable to other proteins, and is active at both proximal and distal positions of target promoters. As such, the EDLL motif is able to partly overcome the repression conferred by the AtHB2 transcription factor, which contains an ERF-associated amphiphilic repression (EAR) motif. We further examined the activation potential of EDLL by analysis of the regulation of flowering time by NF-Y (nuclear factor Y) proteins. Genetic evidence indicates that NF-Y protein complexes potentiate the action of CONSTANS in regulation of flowering in Arabidopsis; we show that the transcriptional activation function of CONSTANS can be substituted by direct fusion of the EDLL activation motif to NF-YB subunits. The EDLL motif represents a potent plant activation domain that can be used as a tool to confer transcriptional activation potential to heterologous DNA-binding proteins.

  6. MOMFER: A Search Engine of Thompson's Motif-Index of Folk Literature

    NARCIS (Netherlands)

    Karsdorp, F.; Meulen, M. van der; Meder, Th.; Bosch, A.P.J. van den

    2015-01-01

    More than fifty years after the first edition of Thompson's seminal Motif-Indexof Folk Literature, we present an online search engine tailored to fully disclose the index digitally. This search engine, called MOMFER, greatly enhances the searchability of the Motif-Index and provides exciting new way

  7. GOmotif: A web server for investigating the biological role of protein sequence motifs

    Directory of Open Access Journals (Sweden)

    He Runtao

    2011-09-01

    Full Text Available Abstract Background Many proteins contain conserved sequence patterns (motifs that contribute to their functionality. The process of experimentally identifying and validating novel protein motifs can be difficult, expensive, and time consuming. A means for helping to identify in advance the possible function of a novel motif is important to test hypotheses concerning the biological relevance of these motifs, thus reducing experimental trial-and-error. Results GOmotif accepts PROSITE and regular expression formatted motifs as input and searches a Gene Ontology annotated protein database using motif search tools. The search returns the set of proteins containing matching motifs and their associated Gene Ontology terms. These results are presented as: 1 a hierarchical, navigable tree separated into the three Gene Ontology biological domains - biological process, cellular component, and molecular function; 2 corresponding pie charts indicating raw and statistically adjusted distributions of the results, and 3 an interactive graphical network view depicting the location of the results in the Gene Ontology. Conclusions GOmotif is a web-based tool designed to assist researchers in investigating the biological role of novel protein motifs. GOmotif can be freely accessed at http://www.gomotif.ca

  8. Genome adaptations of a tripartite motif protein for retroviral defense in cattle and sheep

    Science.gov (United States)

    Tripartite motif (TRIM) genes encode proteins composed of RING, B-box, and coiled coil motif domains. Primate TRIM5' has been shown to be a primary determinant of retroviral host cell range restriction in primates. TRIM5 restriction was originally thought to be a primate-specific defense mechanism...

  9. Dynamic consequences of mutating the typical HPGG motif of apocytochrome b5 revealed by computer simulation

    Institute of Scientific and Technical Information of China (English)

    Ying Wu Lin; Tian Lei Ying; Li Fu Liao

    2009-01-01

    Apecytochrome b5 with a typical heme-binding motif of HPGC,and its variants with mutated motifs,GPGG,GPGH,HVGG,and HPGP,have been subjected to molecular dynamics simulation.Comparison of the dynamic consequences has revealed the crucial role of HPGG in assembling the heme group of cytochrome b5 and in modulating protein structure,property and function.

  10. An Efficient Exact Algorithm for the Motif Stem Search Problem over Large Alphabets.

    Science.gov (United States)

    Yu, Qiang; Huo, Hongwei; Vitter, Jeffrey Scott; Huan, Jun; Nekrich, Yakov

    2015-01-01

    In recent years, there has been an increasing interest in planted (l, d) motif search (PMS) with applications to discovering significant segments in biological sequences. However, there has been little discussion about PMS over large alphabets. This paper focuses on motif stem search (MSS), which is recently introduced to search motifs on large-alphabet inputs. A motif stem is an l-length string with some wildcards. The goal of the MSS problem is to find a set of stems that represents a superset of all (l , d) motifs present in the input sequences, and the superset is expected to be as small as possible. The three main contributions of this paper are as follows: (1) We build motif stem representation more precisely by using regular expressions. (2) We give a method for generating all possible motif stems without redundant wildcards. (3) We propose an efficient exact algorithm, called StemFinder, for solving the MSS problem. Compared with the previous MSS algorithms, StemFinder runs much faster and reports fewer stems which represent a smaller superset of all (l, d) motifs. StemFinder is freely available at http://sites.google.com/site/feqond/stemfinder. PMID:26357225

  11. A Fast Cluster Motif Finding Algorithm for ChIP-Seq Data Sets.

    Science.gov (United States)

    Zhang, Yipu; Wang, Ping

    2015-01-01

    New high-throughput technique ChIP-seq, coupling chromatin immunoprecipitation experiment with high-throughput sequencing technologies, has extended the identification of binding locations of a transcription factor to the genome-wide regions. However, the most existing motif discovery algorithms are time-consuming and limited to identify binding motifs in ChIP-seq data which normally has the significant characteristics of large scale data. In order to improve the efficiency, we propose a fast cluster motif finding algorithm, named as FCmotif, to identify the (l,  d) motifs in large scale ChIP-seq data set. It is inspired by the emerging substrings mining strategy to find the enriched substrings and then searching the neighborhood instances to construct PWM and cluster motifs in different length. FCmotif is not following the OOPS model constraint and can find long motifs. The effectiveness of proposed algorithm has been proved by experiments on the ChIP-seq data sets from mouse ES cells. The whole detection of the real binding motifs and processing of the full size data of several megabytes finished in a few minutes. The experimental results show that FCmotif has advantageous to deal with the (l,  d) motif finding in the ChIP-seq data; meanwhile it also demonstrates better performance than other current widely-used algorithms such as MEME, Weeder, ChIPMunk, and DREME. PMID:26236718

  12. Increased abundance of the adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif (APPL1) in patients with obesity and type 2 diabetes: evidence for altered adiponectin signalling

    OpenAIRE

    Holmes, R.M.; Yi, Z; De Filippis, E.; Berria, R.; S. Shahani; P. Sathyanarayana; Sherman, V.; K. Fujiwara; Meyer, C.; Christ-Roberts, C.; Hwang, H; Finlayson, J.; Dong, L. Q.; Mandarino, L. J.; Bajaj, M.

    2011-01-01

    Aims/hypothesis The adiponectin signalling pathway is largely unknown, but recently the adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif (APPL1), has been shown to interact directly with adiponectin receptor (ADIPOR)1. APPL1 is present in C2C12 myoblasts and mouse skeletal muscle, but its presence in human skeletal muscle has not been investigated. Methods Samples from type 2 diabetic, and lean and non-diabetic obese participants w...

  13. Seed storage protein gene promoters contain conserved DNA motifs in Brassicaceae, Fabaceae and Poaceae

    Directory of Open Access Journals (Sweden)

    Fauteux François

    2009-10-01

    Full Text Available Abstract Background Accurate computational identification of cis-regulatory motifs is difficult, particularly in eukaryotic promoters, which typically contain multiple short and degenerate DNA sequences bound by several interacting factors. Enrichment in combinations of rare motifs in the promoter sequence of functionally or evolutionarily related genes among several species is an indicator of conserved transcriptional regulatory mechanisms. This provides a basis for the computational identification of cis-regulatory motifs. Results We have used a discriminative seeding DNA motif discovery algorithm for an in-depth analysis of 54 seed storage protein (SSP gene promoters from three plant families, namely Brassicaceae (mustards, Fabaceae (legumes and Poaceae (grasses using backgrounds based on complete sets of promoters from a representative species in each family, namely Arabidopsis (Arabidopsis thaliana (L. Heynh., soybean (Glycine max (L. Merr. and rice (Oryza sativa L. respectively. We have identified three conserved motifs (two RY-like and one ACGT-like in Brassicaceae and Fabaceae SSP gene promoters that are similar to experimentally characterized seed-specific cis-regulatory elements. Fabaceae SSP gene promoter sequences are also enriched in a novel, seed-specific E2Fb-like motif. Conserved motifs identified in Poaceae SSP gene promoters include a GCN4-like motif, two prolamin-box-like motifs and an Skn-1-like motif. Evidence of the presence of a variant of the TATA-box is found in the SSP gene promoters from the three plant families. Motifs discovered in SSP gene promoters were used to score whole-genome sets of promoters from Arabidopsis, soybean and rice. The highest-scoring promoters are associated with genes coding for different subunits or precursors of seed storage proteins. Conclusion Seed storage protein gene promoter motifs are conserved in diverse species, and different plant families are characterized by a distinct combination

  14. Identification of the salmon somatolactin receptor, a new member of the cytokine receptor family.

    Science.gov (United States)

    Fukada, Haruhisa; Ozaki, Yuichi; Pierce, Andrew L; Adachi, Shinji; Yamauchi, Kohei; Hara, Akihiko; Swanson, Penny; Dickhoff, Walton W

    2005-05-01

    Somatolactin (SL) is a pituitary hormone of the GH/prolactin (PRL) family that so far has been found only in fish. Compared with GH and PRL, the primary structure of SL is highly conserved among divergent fish species, suggesting it has an important function and a discriminating receptor that constrains structural change. However, SL functions are poorly understood, and receptors for SL have not yet been identified. During cloning of GH receptor cDNA from salmon, we found a variant with relatively high (38-58%) sequence identity to vertebrate GH receptors and low (28-33%) identity to PRL receptors; however, the recombinant protein encoding the extracellular domain showed only weak binding of GH. Ligand binding of the recombinant extracellular domain for this receptor confirmed that the cDNA encoded a specific receptor for SL. The SL receptor (SLR) has common features of a GH receptor including FGEFS motif, six cysteine residues in the extracellular domain, a single transmembrane region, and Box 1 and 2 regions in the intracellular domain. These structural characteristics place the SLR in the cytokine receptor type I homodimeric group, which includes receptors for GH, PRL, erythropoietin, thrombopoietin, granulocyte-colony stimulating factor, and leptin. Transcripts for SLR were found in 11 tissues with highest levels in liver and fat, supporting the notion that a major function of SL is regulation of lipid metabolism. Cloning SLR cDNA opens the way for discovery of new SL functions and target tissues in fish, and perhaps novel members of this receptor family in other vertebrates. PMID:15718271

  15. Characteristic of bending fracture in C/C composite. ; Effect of reinforcement fiber on fracture mechanism. C/C composite no mage hakai tokusei. ; Kyoka sen'i no sai ga hakai ni oyobosu eikyo

    Energy Technology Data Exchange (ETDEWEB)

    Kawada, H.; Hayashi, I. (Waseda Univ., Tokyo (Japan)); Yamamoto, Y.; Yoshida, T.; Ota, I. (Waseda Univ., Tokyo (Japan). Graduate Student)

    1993-03-15

    Three-point bending test is employed as the evaluation method to test C/C composites for which two types of satin weave carbon fiber cloths (T300 and HTA) are used. The load of T300 increases almost linearly and drops rapidly after reaching the maximum load, while that of HTA increases non-linearly and drops gradually after reaching the maximum load. The strength of HTA becomes about 1.9 times that of T300. The three-point bending test carried out in this study is performed in the range where fracture by bending occurs, indicating that the employed span is sufficient. As a result of observation of the inside, it is found that brittle fracture accompanying rupture of longitudinal fibers occurs with T300 while the fracture of HTA is caused by a propagation of a latent microcrack inside HTA selecting the weakest face. The increase in the strength of materials employed for this study is found to be largely dependent on the difference in the mechanical adhesive strength caused by the difference in the sectional shape of the reinforced fibers. 10 refs., 12 figs., 2 tabs.

  16. cWords - systematic microRNA regulatory motif discovery from mRNA expression data

    DEFF Research Database (Denmark)

    Rasmussen, Simon Horskjær; Jacobsen, Anders; Krogh, Anders

    2013-01-01

    -transcriptional regulation by small RNAs is mediated through partial complementary binding to messenger RNAs leaving nucleotide signatures or motifs throughout the entire transcriptome. Computational methods for discovery and analysis of sequence motifs in high-throughput mRNA expression profiling experiments are becoming...... increasingly important tools for the identification of post-transcriptional regulatory motifs and the inference of the regulators and their targets. RESULTS:cWords is a method designed for regulatory motif discovery in differential case-control mRNA expression datasets. We have improved the algorithms...... and statistical methods of cWords, resulting in at least a factor 100 speed gain over the previous implementation. On a benchmark dataset of 19 microRNA (miRNA) perturbation experiments cWords showed equal or better performance than two comparable methods, miReduce and Sylamer. We have developed rigorous motif...

  17. MOTIFSIM: A web tool for detecting similarity in multiple DNA motif datasets.

    Science.gov (United States)

    Tran, Ngoc Tam L; Huang, Chun-Hsi

    2015-07-01

    Currently, there are a number of motif detection tools available that possess unique functionality. These tools often report different motifs, and therefore use of multiple tools is generally advised since common motifs reported by multiple tools are more likely to be biologically significant. However, results produced by these different tools need to be compared and existing similarity detection tools only allow comparison between two data sets. Here, we describe a motif similarity detection tool (MOTIFSIM) possessing a web-based, user-friendly interface that is capable of detecting similarity from multiple DNA motif data sets concurrently. Results can either be viewed online or downloaded. Users may also download and run MOTIFSIM as a command-line tool in stand-alone mode. The web tool, along with its command-line version, user manuals, and source codes, are freely available at http://biogrid-head.engr.uconn.edu/motifsim/. PMID:26156781

  18. RSAT::Plants: Motif Discovery Within Clusters of Upstream Sequences in Plant Genomes.

    Science.gov (United States)

    Contreras-Moreira, Bruno; Castro-Mondragon, Jaime A; Rioualen, Claire; Cantalapiedra, Carlos P; van Helden, Jacques

    2016-01-01

    The plant-dedicated mirror of the Regulatory Sequence Analysis Tools (RSAT, http://plants.rsat.eu ) offers specialized options for researchers dealing with plant transcriptional regulation. The website contains whole-sequenced genomes from species regularly updated from Ensembl Plants and other sources (currently 40), and supports an array of tasks frequently required for the analysis of regulatory sequences, such as retrieving upstream sequences, motif discovery, motif comparison, and pattern matching. RSAT::Plants also integrates the footprintDB collection of DNA motifs. This protocol explains step-by-step how to discover DNA motifs in regulatory regions of clusters of co-expressed genes in plants. It also explains how to empirically control the significance of the result, and how to associate the discovered motifs with putative binding factors. PMID:27557774

  19. Selection for the G4 DNA motif at the 5' end of human genes.

    Science.gov (United States)

    Eddy, Johanna; Maizels, Nancy

    2009-04-01

    Formation of G4 DNA may occur in the course of replication and transcription, and contribute to genomic instability. We have quantitated abundance of G4 motifs and potential for G4 DNA formation of the nontemplate strand of 5' exons and introns of transcripts of human genes. We find that, for all human genes, G4 motifs are enriched in 5' regions of transcripts relative to downstream regions; and in 5' regulatory regions relative to coding regions. Notably, although tumor suppressor genes are depleted and proto-oncogenes enriched in G4 motifs, abundance of G4 motifs in the 5' regions of transcripts of genes in these categories does not differ. These results support the hypothesis that G4 motifs are under selection in the human genome. They further show that for tumor suppressor genes and proto-oncogenes, independent selection determines potential for G4 DNA formation of 5' regulatory regions of transcripts and downstream coding regions.

  20. The Land of the Dead – International Motifs in the Oldest Work of Japanese Literature

    Directory of Open Access Journals (Sweden)

    Danijela Vasić

    2010-02-01

    Full Text Available Il existe dans le Kojiki (712, la plus ancienne œuvre littéraire du Japon, une abondance de motifs que l’on peut retrouver dans les cultures de nombreux peuples dans le monde entier. Cet article traite des motifs internationaux tissés dans deux mythes du premier tome, formant une image poétique du Pays des morts, la partie souterraine d’une structure cosmique tripartite. Sont abordés, entre autres, le motif largement connu de Perséphone, le motif orphique ou encore le motif de la fuite du Pays des morts.In the Kojiki (712, the oldest literary work of Japan, there is a plethora of motifs which could be found in the cultures of many peoples all over the world. This paper deals with the international motifs interwoven in two myths from the first volume, forming a poetic picture of the Land of the Dead, the underworld part of the trichotomic cosmic structure. Among other things, we find the widely known Persephone motif, the Orphic motif or the motif of the successful escape from the Land of the Dead.En Kojiki (712, la obra literaria más antigua de Japón, abundan motivos que pueden encontrarse en numerosas culturas de todo el mundo. Este artículo analiza los motivos internacionales entretejidos en dos mitos del primer volumen, los cuales forman una imagen poética del País de los Muertos, la sección subterránea de una estructura cósmica tripartita. Se abordan, entre otros, el famoso motivo de Perséfone, el motivo órfico de la huída exitosa del País de los Muertos.